Lasers Med Sci. 2016 Mar 16. [Epub ahead of print]

808-nm laser therapy with a flat-top handpiece photobiomodulates mitochondria activities of Paramecium primaurelia (Protozoa).

Amaroli A1, Ravera S2, Parker S3, Panfoli I2, Benedicenti A3, Benedicenti S4.

Author information

  • 1Department of Earth, Environmental and Life Sciences, Protistology Laboratory, University of Genoa, Corso Europa, 26, 16132, Genoa, Italy.
  • 2Department of Pharmacy, Biochemistry Laboratory, University of Genoa, Viale Benedetto XV, 3, 16132, Genoa, Italy.
  • 3Department of Surgical Sciences and Integrated Diagnostic, University of Genoa, Largo R. Benzi, 10, 16132, Genoa, Italy.
  • 4Department of Surgical Sciences and Integrated Diagnostic, University of Genoa, Largo R. Benzi, 10, 16132, Genoa, Italy.


Photobiomodulation is proposed as a non-linear process, and only low-level laser therapy (LLLT) is assumed to stimulate exposed cells, whereas high powered laser and fluences can cause negative effects, exhausting the cell’s energy reserve as a consequence of excessive photon-based stimulation. In our work, we investigated and compared the effects of 808-nm diode laser (CW) with a new flat-top handpiece. To this purpose, we tested the photobiomodulation effects of 1 and 3 J/cm2 fluence, both generated by 100 mW or 1 W of laser power and of 64 J/cm2 of fluence generated by 100 mW, 1 W, 1.5 W or 2 W, as expressed through oxygen consumption and ATP synthesis of Paramecium. Data collected indicates the incremental consumption of oxygen through irradiation with 3 J/cm2-100 mW or 64 J/cm2-1 W correlates with an increase in Paramecium ATP synthesis. The Paramecium respiration was inhibited by fluences 64 J/cm2-100 mW or 64 J/cm2-2 W and was followed by a decrease in the endogenous ATP concentration. The 1 J/cm2-100 mW or 1 W and 3 J/cm2-1 W did not affect mitochondrial activity. The results show that the fluence of 64 J/cm2-1 W more than the 3 J/cm2-100 mW causes greater efficiency in Paramecium mitochondria respiratory chain activity. Our results suggest that thanks to flat-top handpiece we used, high fluences by high-powered laser have to be reconsidered as an effective and non-invasive therapy. Possible associated benefits of deeper tissue penetration would increase treatment effectiveness and reduced irradiation time.

Altern Lab Anim. 2015 Jul;43(3):155-62.

The protozoan, Paramecium primaurelia, as a non-sentient model to test laser light irradiation: The effects of an 808nm infrared laser diode on cellular respiration.

Amaroli A1, Ravera S2, Parker S3, Panfoli I2, Benedicenti A3, Benedicenti S3.

Author information

  • 1Department of Earth, Environmental and Life Sciences, Protistology Laboratory, University of Genoa, Genoa, Italy.
  • 2Department of Pharmacy, Biochemistry Laboratory, University of Genoa, Genoa, Italy.
  • 3Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.


Photobiomodulation (PBM) has been used in clinical practice for more than 40 years. Unfortunately, conflicting literature has led to the labelling of PBM as a complementary or alternative medicine approach. However, past and ongoing clinical and research studies by reputable investigators have re-established the merits of PBM as a genuine medical therapy, and the technique has, in the last decade, seen an exponential increase in the numbers of clinical instruments available, and their applications. This resurgence has led to a clear need for appropriate experimental models to test the burgeoning laser technology being developed for medical applications. In this context, an ethical model that employs the protozoan, Paramecium primaurelia, is proposed. We studied the possibility of using the measure of oxygen consumption to test PBM by irradiation with an infrared or near-infrared laser. The results show that an 808nm infrared laser diode (1W; 64J/cm2) affects cellular respiration in P. primaurelia, inducing, in the irradiated cells, a significantly (p < 0.05) increased oxygen consumption of about 40%. Our findings indicate that Paramecium can be an excellent tool in biological assays involving infrared and near-infrared PBM, as it combines the advantages of in vivo results with the practicality of in vitro testing. This test represents a fast, inexpensive and straightforward assay, which offers an alternative to both traditional in vivo testing and more expensive mammalian cellular cultures.

Photomed Laser Surg. 2015 Jan 2. [Epub ahead of print]

Paramecium: A Promising Non-Animal Bioassay to Study the Effect of 808?nm Infrared Diode Laser Photobiomodulation.

Amaroli A1, Parker S, Dorigo G, Benedicenti A, Benedicenti S.

Author information

  • 11 Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa , Genoa, Italy .


Abstract Objective: Photobiostimulation and photobiomodulation (PBM) are terms applied to the manipulation of cellular behavior using low intensity light sources, which works on the principle of inducing a biological response through energy transfer. The aim of this investigation was to identify a laboratory assay to test the effect of an infrared diode laser light (808 nm) on cell fission rate.

Materials and methods: Sixty cells of Paramecium primaurelia were divided in two groups of 30. The first group (test group) was irradiated, at a temperature of 24°C, for 50 sec by a 808 nm diode laser with a flat top handpiece [1 cm of spot diameter, 1 W in continuous wave (CW), 50 sec irradiation time, 64 J/cm2 of fluence]. The second group (control group) received no laser irradiation. All cells were transferred onto a depression slide, fed, and incubated in a moist chamber at a temperature of 24°C. The cells were exposed and monitored for 10 consecutive fission rates. Changes in temperature and pH were also evaluated.

Results: The exposed cells had a fission rate rhythm faster than the control cells, showing a binary fission significantly (p<0.05) shorter than unexposed cells. No significant effects of laser irradiation on pH and temperature of Paramecium’s lettuce infusion medium were observed.

Conclusions: The 808 nm infrared diode laser light, at the irradiation parameters used in our work, results in a precocious fission rate in P. primaurelia cells, probably through an increase in metabolic activity, secondary to an energy transfer.




Dermatol Surg. 2014 Dec 4. [Epub ahead of print]

Light-Emitting Diode-Generated Red Light Inhibits Keloid Fibroblast Proliferation.

Mamalis A1, Jagdeo J.

Author information

  • 1*Department of Dermatology, University of California at Davis, Sacramento, California; †Dermatology Service, Sacramento VA Medical Center, Mather, California; ‡Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York.



Red light is part of the visible light spectrum that does not generate DNA adducts associated with skin cancer and photoaging and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode-generated red light (LED-RL) inhibits proliferation of skin fibroblasts. The effects of LED-RL on keloidal skin are not well characterized.


To determine the effect of LED-RL on keloid-derived fibroblast proliferation and viability in vitro.


Irradiation of primary keloid-derived human skin fibroblasts using LED-RL panels was performed in vitro, and modulation of proliferation and viability was quantified using trypan blue dye exclusion assay. Statistical analysis was performed using analysis of variance to compare treatment arms and the Student t-test to compare each treatment arm with the paired bench control arm.


Keloid fibroblasts treated with LED-RL 240, 320, and 480 J/cm demonstrated statistically significant dose-dependent decreases in relative proliferation rate of 12.4%, 16.5%, and 28.9%, respectively, compared with matched nonirradiated controls (p < .05) and did not significantly alter viability relative to the matched nonirradiated controls.


Light-emitting diode-generated red light can inhibit keloid fibroblast proliferation in a dose-dependent manner without altering viability. Light-emitting diode-generated red light has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.

 2013 Jan-Feb;(772):44-5.

Scars and lasers.

[Article in French]

Author information

  • 1Centre Laser de L'Arche Jacques Coeur, France.


Different lasers are used to improve scars in combination with other therapies. The pulsed dye laser is considered to be the gold standard for hypertrophic scars and keloids. Ablative laser treatments are used with atrophic scars. Ablative or non-ablative fractional laser treatments are developing rapidly due to the lower risk of infection and easier follow-up care.


Photomed Laser Surg. 2010 Aug;28 Suppl 1:S151-6. doi: 10.1089/pho.2008.2475.

Lowlevel laser irradiation (InGaAlP-660 nm) increases fibroblast cell proliferation and reduces cell death in a dose-dependent manner.

Frigo L1, Fávero GM, Lima HJ, Maria DA, Bjordal JM, Joensen J, Iversen VV, Marcos RL, Parizzoto NA, Lopes-Martins RA.

Author information

  • 1Biological Sciences and Health Center, Cruzeiro do Sul University, São Paulo, Brazil.



Impaired cell metabolism and increased cell death in fibroblast cells are physiological features of chronic tendinopathy. Although several studies have shown that lowlevel laser therapy (LLLT) at certain parameters has a biostimulatory effect on fibroblast cells, it remains uncertain if LLLT effects depend on the physiological state.


High-metabolic immortal cell culture and primary human keloid fibroblast cell culture were used in this study. Trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test were used to determine cell viability and proliferation. Propidium iodide stain was used for cell-cycle analysis by flow cytometry. Laser irradiation was performed daily on three consecutive days with a GaAlAs 660-nm laser (mean output: 50 mW, spot size 2 mm(2), power density =2.5 W/cm(2)) and a typical LLLT dose and a high LLLT dose (irradiation times: 60 or 420 s; fluences:150 or 1050 J/cm(2); energy delivered: 3 or 21 J).


Primary fibroblast cell culture from human keloids irradiated with 3 J showed significant proliferation by the trypan blue exclusion test (p < 0.05), whereas the 3T3 cell culture showed no difference using this method. Propidium iodide staining flow cytometry data showed a significant decrease in the percentage of cells being in proliferative phases of the cell cycle (S/g(2)/M) when irradiated with 21 J in both cell types (hypodiploid cells increased).


Our data support the hypothesis that the physiological state of the cells affects the LLLT results, and that high-metabolic rate and short- cell-cycle 3T3 cells are not responsive to LLLT. In conclusion, LLLT with a dose of 3 J reduced cell death significantly, but did not stimulate cell cycle. A LLLT dose of 21 J had negative effects on the cells, as it increased cell death and inhibited cell proliferation.


Photomed Laser Surg. 2010 Jun;28(3):417-22. doi: 10.1089/pho.2009.2548.

Effects of lowlevel laser therapy on pain and scar formation after inguinal herniation surgery: a randomized controlled single-blind study.

Carvalho RL1, Alcântara PS, Kamamoto F, Cressoni MD, Casarotto RA.

Author information

  • 1Postgraduate Program in Rehabilitation Sciences, University of São Paulo, São Paulo, Brazil.



The aim of this study was to investigate the efficacy of an infrared GaAlAs laser operating with a wavelength of 830 nm in the postsurgical scarring process after inguinal-hernia surgery.


Lowlevel laser therapy (LLLT) has been shown to be beneficial in the tissue-repair process, as previously demonstrated in tissue culture and animal experiments. However, there is lack of studies on the effects of LLLT on postsurgical scarring of incisions in humans using an infrared 830-nm GaAlAs laser.


Twenty-eight patients who underwent surgery for inguinal hernias were randomly divided into an experimental group (G1) and a control group (G2). G1 received LLLT, with the first application performed 24 h after surgery and then on days 3, 5, and 7. The incisions were irradiated with an 830-nm diode laser operating with a continuous power output of 40 mW, a spot-size aperture of 0.08 cm(2) for 26 s, energy per point of 1.04 J, and an energy density of 13 J/cm(2). Ten points per scar were irradiated. Six months after surgery, both groups were reevaluated using the Vancouver Scar Scale (VSS), the Visual Analog Scale, and measurement of the scar thickness.


G1 showed significantly better results in the VSS totals (2.14 +/- 1.51) compared with G2 (4.85 +/- 1.87); in the thickness measurements (0.11 cm) compared with G2 (0.19 cm); and in the malleability (0.14) compared with G2 (1.07). The pain score was also around 50% higher in G2.


Infra-red LLLT (830 nm) applied after inguinal-hernia surgery was effective in preventing the formation of keloids. In addition, LLLT resulted in better scar appearance and quality 6 mo postsurgery.


Acta Cir Bras. 2011 Feb;26(1):25-30.

In vitro effect of 470 nm LED (Light Emitting Diode) in keloid fibroblasts.

Bonatti S1, Hochman B, Tucci-Viegas VM, Furtado F, Pinfildi CE, Pedro AC, Ferreira LM.

Author information

  • 1Department of Surgery, UNIFESP, Sao Paulo, SP, Brazil.



To quantify keloid fibroblasts after irradiation with 470nm blue LED, in vitro.


Fibroblasts from keloid and adjacent skin have been obtained from 6 patients. Cells have been cultivated and maintained in DMEM culture medium. In Petri dishes, they were irradiated with energy doses of 6J, 12J and 18J. After 24 h, counting was done by the average of the triplicates for each sample.


There were no significant differences in the number of irradiated keloid fibroblasts at the studied doses (p=0.261). In adjacent skin fibroblasts, differences were observed (p=0.025) concerning the doses of 18 J and 6 J (p=0.03).


There was a reduction in the number of adjacent skin fibroblasts irradiated with 470nm blue LED at the energy dose of 18 J compared to the ones irradiated at the energy dose of 6 J. There were no changes in keloid fibroblasts counting at any of the doses applied, 24 h after irradiation.

Indian J Dermatol Venereol Leprol. 2005 Jan-Feb;71(1):31-4.

Efficacy of diode laser for treating acne keloidalis nuchae.

Shah GK1.

Author information

  • 1The Skin and Laser Centre, Mumbai, Maharashtra, India.


Acne keloidalis nuchae is usually treated with oral antibiotics, local antiseptics or intralesional steroids but with limited success. I assessed the efficacy of diode laser for treating the inflammatory and keloidal papules of acne keloidalis nuchae in two cases. The lesions in both the cases showed about 90 to 95% clearance after 4 treatment sessions at one to one and half month intervals. No new lesions were observed during the follow up period of six months after the last laser treatment. Thus, after clearing bacterial infection, laser hair epilation can be used as the first line of therapy for treating papules of acne keloidalis nuchae. This is the first attempt at treating acne keloidalis nuchae with a diode laser.


Coronary Artery Laser Blood Irradiation

Photomed Laser Surg. 2014 Oct;32(10):582-587.

Effects of Intravascular Low-Level Laser Therapy During Coronary Intervention on Selected Growth Factors Levels.

Derkacz A1, Protasiewicz M, Rola P, Podgorska K, Szymczyszyn A, Gutherc R, Por?ba R, Doroszko A.

Author information

  • 11 Department of Internal Medicine and Hypertension, Wroclaw Medical University , Wroclaw, Poland .


Abstract Objective: The objective of this study was to evaluate the effect of intravascular low-level laser therapy (LLLT) on selected growth factor levels in subjects undergoing percutaneous coronary interventions (PCI).

Background data: Restenosis remains the main problem with the long-term efficacy of PCI, and growth factors are postulated to play a crucial role in the restenosis cascade.

Materials and methods: In a randomized prospective study, an 808 nm LLLT (100 mW/cm2, continuous wave laser, 9 J/cm2, illuminated area 1.6-2.5 cm2) was delivered intracoronarily to patients during PCI. Fifty-two patients underwent irradiation with laser light, and 49 constituted the control group. In all individuals, serum levels of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and fibroblast growth factor-2 (FGF-2) were measured before angioplasty, then 6 and 12 h and 1 month after the procedure. In all patients, a control angiography was performed 6 months later.

Results: There were no significant differences in IGF-1 and VEGF levels between the groups. While evaluating FGF-2, we observed its significantly lower levels in the irradiated patients during each examination. There was a significant increase in TGF-β1 level in control group after 12 h of observation. In the irradiated individuals, control angiography revealed smaller late lumen loss and smaller late lumen loss index as compared with the control group. The restenosis rate was 15.0% in the treated group, and 32.4% in the control group, respectively.

Conclusions: LLLT decreases levels of TGF-β1 and FGF-2 in patients undergoing coronary intervention, which may explain smaller neointima formation.

Lasers Med Sci.  2012 Jun 26. [Epub ahead of print]

Effect of the intravascular low energy laser illumination during percutaneous coronary intervention on the inflammatory process in vascular wall.

Derkacz A, Protasiewicz M, Porba R, Doroszko A, Andrzejak R.


Department of Internal Medicine, Occupational Diseases and Hypertension, Wroclaw Medical University, Borowska 213 Street, 50-556, Wroclaw, Poland,


The angioplasty procedure is associated with a release of numerous factors triggering the local inflammatory reaction in vascular wall and leading thus to the restenosis. In this study, we hypothesize that the low-energy laser irradiation may exert beneficial effect by limiting this process. A group of 101 subjects (75 men and 26 women, mean age: 59.1±10.3) treated with percutaneous coronary intervention (PCI), were recruited to this study. While 52 patients (40 men and 12 women) were subjected to the intravascular low-energy laser irradiation (808 nm) of dilated lesion during the PCI, the remaining patients (35 men and 14 women) constituted the control group. The levels of interleukin 1, 6 and 10 (IL 1, IL 6 and IL 10) were measured immediately before the procedure, and then at the 6th, 12th hour as well as after 1 month following the PCI. Significantly lower levels of IL 1 and IL 6 in the irradiated group during each analysis after the procedure were observed. Moreover, significantly lower IL 10 level in irradiated group within 6 and 12 hours after PCI was observed. Irradiation of the lesion with low-energy laser radiation during the PCI procedure results in a decrease in the levels of pro-inflammatory IL 1 and IL 6 as well as in an increase in the levels of anti-inflammatory IL 10, which may result in decreased risk for restenosis.


Post Herpetic Neuralgia – Herpes

Clin J Pain. 2013 Oct;29(10):e6-9. doi: 10.1097/AJP.0b013e31828b8ef8.

Postherpetic neuralgia: case study of class 4 laser therapy intervention.

Knapp DJ.



Postherpetic neuralgia (PHN) is a neuropathic sequelae in 8% to 27% of individuals with prior varicella zoster virus infection and herpes zoster resulting in retrograde demyelination, neurotoxic reactive oxygen species levels, and proinflammatory cytokine activation of microglia. Pain management strategies are well documented, but not always effective. Laser therapy has shown utility in nerve injury-related pain disorders and was considered a potentially efficacious intervention.


Case report.


Class 4 therapeutic laser treatment was applied with a dual wavelength GaAlAs (810 nm), GaAl (980 nm) laser, 2 to 4 W, 50% duty cycle, 10 Hz pulse active phase, 2.5 cm diameter aperture, scanning technique with skin contact, 10-minute treatment, 600 to 1200 J total, energy density of 3.5 to 7.1 J/cm average per session, and power density from 0.41 to 0.82 W/cm for 8 treatments. Outcome measures included the Neuropathy Pain Scale Questionnaire as the primary outcome measure, with the Numeric Pain Scale and total area of allodynia touch sensitivity as secondary outcome measurements.


The author reports a case of PHN of 15-year duration resistant to prior interventions. Weekly laser therapy treatment over 8 weeks resulted in reduced 0 to 10 Numeric Pain Scale score from 8 to 0, Neuropathy Pain Scale Questionnaire total score from 39 to 4, and allodynia over a 60 cm surface area of the upper trunk and posterior arm totally resolved, with resolution continued at 14-month follow-up.


Theoretically, laser therapy induced tissue changes in this case occurring at and below the skin surface altering inflammatory and excitatory peripheral mechanisms noted to take place in the PHN patient. Peripheral nociceptor firing must be brought back to normal thresholds to resolve such chronic neuropathic pain and inhibit the possible central sensitization component. Anti-inflammatory cytokines, growth factors, nitric oxide, adenosine triphosphate (ATP), and other mechanisms stimulated by laser therapy as noted in medical literature may be central to the favorable response seen in this patient. Controlled clinical trials of class 4 laser therapy in the PHN patient population with similar doses would be beneficial to determine if this is an effective treatment option in PHN.

Lasers Med Sci.  2013 Apr 13. [Epub ahead of print]

Laser treatment of recurrent herpes labialis: a literature review.

de Paula Eduardo C, Aranha AC, Simões A, Bello-Silva MS, Ramalho KM, Esteves-Oliveira M, de Freitas PM, Marotti J, Tunér J.


Special Laboratory of Lasers in Dentistry (LELO), Department of Restorative Dentistry, School of Dentistry of the University of São Paulo (USP), Av. Prof. Lineu Prestes, 2227, 05508-000, São Paulo, SP, Brazil,


Recurrent herpes labialis is a worldwide life-long oral health problem that remains unsolved. It affects approximately one third of the world population and causes frequent pain and discomfort episodes, as well as social restriction due to its compromise of esthetic features. In addition, the available antiviral drugs have not been successful in completely eliminating the virus and its recurrence. Currently, different kinds of laser treatment and different protocols have been proposed for the management of recurrent herpes labialis. Therefore, the aim of the present article was to review the literature regarding the effects of laser irradiation on recurrent herpes labialis and to identify the indications and most successful clinical protocols. The literature was searched with the aim of identifying the effects on healing time, pain relief, duration of viral shedding, viral inactivation, and interval of recurrence. According to the literature, none of the laser treatment modalities is able to completely eliminate the virus and its recurrence. However, laser phototherapy appears to strongly decrease pain and the interval of recurrences without causing any side effects. Photodynamic therapy can be helpful in reducing viral titer in the vesicle phase, and high-power lasers may be useful to drain vesicles. The main advantages of the laser treatment appear to be the absence of side effects and drug interactions, which are especially helpful for older and immunocompromised patients. Although these results indicate a potential beneficial use for lasers in the management of recurrent herpes labialis, they are based on limited published clinical trials and case reports. The literature still lacks double-blind controlled clinical trials verifying these effects and such trials should be the focus of future research.

Rev Soc Bras Med Trop.  2011 May-Jun;44(3):397-9.

Recurrent herpes simplex infections: laser therapy as a potential tool for long-term successful treatment.

Ferreira DC, Reis HL, Cavalcante FS, Santos KR, Passos MR.


Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.


Herpes simplex virus types 1 and 2 are the main infectious agents associated with oral and genital ulcerations. These infections are now widely recognized as sexually transmitted diseases. Among treatment options, low-level laser therapy (LLLT) has shown promising clinical results as a longer-lasting suppression therapy. Two clinical cases are described with recurrent labial herpes for which LLLT was used. Following treatment, both patients remained symptom free during the 17-month clinical follow-up period.

Photomed Laser Surg.  2011 Nov 2. [Epub ahead of print]

The Effect of 670-nm Low Laser Therapy on Herpes Simplex Type 1.

Muñoz Sanchez PJ, Capote Femenías JL, Díaz Tejeda A, Tunér J.


1 Leonardo Fernández Sánchez Dental Clinic , Cienfuegos, Cuba .


Abstract Objective: The purpose of this work was to study the effect of low-level laser therapy (LLLT) on the healing and relapse intervals in patients with recurrent labial herpes simplex infections.

Background data: Several pharmaceuticals are available to reduce symptoms and improbé healing of labial herpes, but only LLLT has been reported to significantly influence the length of the recurrence period.

Material and methods: In an initial study, 232 patients with herpes simplex type 1 virus symptoms were consecutively selected for either LLLT or conventional therapy, including acyclovir cream or tablets. One of the dentists was responsible for the diagnosis, a second dentist for the treatment, and and a third for the evaluation, to allow for a semi-blinded procedure. Patients in the laser group received 670-nm laser irradiation, 40?mW, 1.6?J, 2.04?J/cm(2), 51?mW/cm(2) per blister in the prodromal stage and 4.8?J in the crust and secondarily infected stages, plus 1.2?J at the C2-C3 vertebrae. Patients were monitored daily during the first week to control healing, and monthly for 1 year to check on recurrence. In a consecutive study, 322 patients receiving LLLT were followed during 5 years to observe the period of ocurrences.

Results: An obvious effect of LLLT was found for both initial healing and for the length of the recurrence periods.

Conclusions: LLLTof herpes simples virus 1 (HSV-1) appears to be an effective treatment modality without any observed side effects.

Cutis.  2011 Sep;88(3):140-8.

Phototherapy in the treatment of cutaneous herpesvirus manifestations.

Kelley JP, Rashid RM.


University of Texas Medical School at Houston, USA.


There is a considerable need for effective and safe treatment of cutaneous herpesvirus lesions. Current common approaches are limited to expensive or multidose oral pills. This systematic review of evidence-based approaches to phototherapy for the various manifestations of the herpesvirus discusses original publications of controlled clinical trials and case reports that were identified through searches in PubMed, MEDLINE, and Ovid. Interventions included photodynamic therapy (PDT), UV light, and near-infrared lasers. Nearly all studies (10 of 11) saw reduction of most or all lesions and extended time before reactivation of the virus. Side effects often were minimal to nonexistent, usually mild erythema at sites of phototreatment. Serious side effects included first-degree burns and linear IgA dermatosis, which were not common. Evidence from the reviewed literature indicates that short-term efficacy from treatment with phototherapy is the most likely outcome. However, long-term effects and follow-up of this treatment modality are lacking but appear promising. We recommend future studies to include more patients, determine the most effective type of phototherapy, and assess long-term follow-up. Furthermore, light-based therapies can be considered a reasonable alternative in situations that preclude traditional drug-based therapies.

Rev Soc Bras Med Trop.  2011 Jun;44(3):397-9.

Recurrent herpes simplex infections: laser therapy as a potential tool for long-term successful treatment.

Ferreira DC, Reis HL, Cavalcante FS, Santos KR, Passos MR.


Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ.


Herpes simplex virus types 1 and 2 are the main infectious agents associated with oral and genital ulcerations. These infections are now widely recognized as sexually transmitted diseases. Among treatment options, low-level laser therapy (LLLT) has shown promising clinical results as a longer-lasting suppression therapy. Two clinical cases are described with recurrent labial herpes for which LLLT was used. Following treatment, both patients remained symptom free during the 17-month clinical follow-up period.

Photomed Laser Surg. 2010 Feb;28(1):135-9.

Low- and high-intensity lasers in the treatment of herpes simplex virus 1 infection.

Bello-Silva MS, de Freitas PM, Aranha AC, Lage-Marques JL, Simões A, de Paula Eduardo C.

Center of Research, Teaching and Clinics of Lasers in Dentistry, University of São Paulo, São Paulo, SP, Brazil.


Herpes simplex virus (HSV) is one of the most common viral infections of the human being. Although most of the seropositive persons do not manifest symptoms, infected individuals may present recurrent infections, characterized by cold sores. HSV-1 infection can result in potentially harmful complications in some patients, especially in those with compromised immunity. We report a clinical case of a patient with severe oral HSV-1 infection in the lower lip. The treatment of the lesions with the association of high-intensity (erbium-doped yttrium aluminum garnet, 2.94 mum, 80 mJ/pulse, 2-4 Hz) and low-intensity (indium gallium aluminum phosphide, 660 nm, 3.8 J/cm(2), 10 mW) lasers has not been reported in the literature. During treatment, no systemic or topical medication was used. Pain sensitivity was completely gone after the first irradiation with the low-intensity laser. During the healing process, lesions were traumatized twice, on the days 4 and 7. Even though the lesions were completely healed within 10 days.

Lasers Med Sci. 2010 May;25(3):397-402. Epub 2009 Aug 11.

Effect of laser phototherapy on recurring herpes labialis prevention: an in vivo study.

de Carvalho RR, de Paula Eduardo F, Ramalho KM, Antunes JL, Bezinelli LM, de Magalhães MH, Pegoretti T, de Freitas PM, de Paula Eduardo C.

Special Laboratory of Lasers in Dentistry, Department of Restorative Dentistry, School of Dentistry, University of São Paulo, São Paulo 05508-000, SP, Brazil.


Alternative treatment for recurrent labial infection by herpes simplex virus (HSV) have been considered. The aim of this study was to evaluate the effectiveness of laser phototherapy in prevention and reduction of severity of labial manifestations of herpes labialis virus. Seventy-one patients, divided into experimental (n = 41) and control (n = 30) groups were followed up for 16 months. Patients in the control group were treated topically with aciclovir and patients in the experimental group were subjected to laser phototherapy (one session per week, 10 weeks): 780 nm, 60 mW, 3.0 J/cm(2) or 4.5 J/cm(2) on healthy (no HSV-1 infection) and affected (with HSV-1 infection) tissues. Patients in the experimental group presented a significant decrease in dimension of herpes labialis lesions (P = 0.013) and inflammatory edema (P = 0.031). The reduction in pain level (P = 0.051) and monthly recurrences (P = 0.076) did not reach statistical significance. This study represents an in vivo indication that this treatment should be further considered as an effective alternative to therapeutic regimens for herpes labialis lesions.

Clin Exp Dermatol. 2006 Sep;31(5):638-41. Epub 2006 Jun 15.

A randomised double-blind study comparing the effect of 1072-nm light against placebo for the treatment of herpes labialis.

Hargate G.

Newlands Medical Centre, Borough Road, Middlesbrough, UK.

BACKGROUND: Previous research demonstrated that 1072-nm narrowband laser light is effective in the treatment of cold sores. AIM: To evaluate the efficacy of an over-the-counter cold-sore treatment device (Virulite CS) incorporating 1072-nm light-emitting diodes. METHODS: A randomised, prospective, double-blind, self-reported study was performed to compare the efficacy of at least six 3-min treatments of 1072-nm narrowband light against placebo, in the treatment of herpes labialis. RESULTS: The 1072-nm light-emitting diode device reduced cold-sore healing time to 6.3 days compared with 9.4 days for placebo (P=0.048). The time the cold sore took to form a crust was also reduced from 2.00 days for those treated with 1072-nm light, compared with 2.88 days for placebo (P=0.059) CONCLUSIONS: The significant difference between the mean healing times in the two groups demonstrates that the Virulite CS device is an effective means of treating herpes labialis.

Used by the kind permission of the Czech Society for the Use of Laser in Medicine,

Laser Therapy of Human Herpes Simplex Lesions

Arturo Guerra Alfonso, Pedro José MuZoz

Clinic “Leonardo Fernández Sánchez“, Cienfuengos, Cuba


Herpes Simplex is rather a widespread illness caused by human herpes virus generally combining primary lesions with periods of latency. The authors evaluate results of treatment with a low power laser and with classical antivirals. Obtained results are demonstrated in attached tables.

By way of illustration the editor also attached a series of images showing typical history of a herpes lesion treated with a laser.


Herpes Simplex is an illness caused by the human herpes virus types 1 and 2 that generally present a primary lesion, with periods of latency and a tendency to relapse. It is also known as Button of fever or Bladder of fever. According to the World Health Organisation (WHO) an international prevalence of about 60 % is observed (1, 2).

An experimental study was carried out, where 232 patients affected by the Herpes Simplex type 1 virus were treated. All patients attended the clinic „Leonardo Fernández“ in Cienfuengos during the period of January 2001 to January 2003, with the objective of determining the time of recurrence of labial herpes in the groups, studied before and after treatment, and to evaluate the effectiveness of low power laser in the treatment of the infection of the virus.


Two groups were selected (study and control) with 116 patients in each group, distributed and classified according to the clinical stage in which they went to consultation. In the study group the patients were offered treatment with a GaAlAs diode laser (670 nm / 30 mW – 40 sec) in the prodromal stage and the stage of vesicles; or (670 nm /20 mW – 2 min) in the crust stage and in infections infected secondarily. To all these patients radiation among vertebras C2 – C3, where the resident ganglion of the virus is located during the latent periods (670 nm / 30 mW – 30 sec), was also applied.

Control group was offered indicated treatment with antivirals (Aciclovir in cream and in pills) and other paliative therapies.

After having carried out the analysis of the data obtained, the following results were obtained:

Study groupn = 116 Recurrence frequency
Once a month Every2 to 3 m Every4 to 5 m Every 6 months Once a year First time norecurrence
Before treatment 9 26 58 12 7 4 0
After treatment 0 0 37 22 25 0 32

Table 1: Patients of the study group, distribution according to the frequency of annual recurrence of the labial herpes before and after laser therapy.

When analysing Table 1 it is observed that the groups of patients suffering from herpes with high frequencies of recurrence (after being treated with laser an waiting one year prior to evaluation of the effectiveness) reported recurrence for more elongated periods of time and 32 patients did not even have any more recurrence.

Controlgroupn = 116 Recurrence frequency after receiving treatment
Once a month Every2 to 3 m Every4 to 5 m Every 6 months Once a year First time norecurrence
Before treatment 7 24 56 14 9 6 0
After treatment 6 21 46 27 14 0 2

Table 2: Patients of the control group, distribution according to the annual recurrence frequency of labial herpes before and after treatment.

In Table 2 the same previous aspects are reflected but in the control group. As it can be observed the cases diminished in number, although discreetely; those that presented more recurrence and of equal number of recurrencies increased in number of patients in the periods of more lingering recurrence. In this group 2 patients reported not having had any more lesions during the analyzed year.

  Recurrence frequency after receiving treatment
Once a month Every2 to 3 m Every4 to 5 m Every 6 months Once a year norecurrence
Study group (n = 116) 0 0 37 22 25 32
Control group (n = 116) 6 21 46 27 14 2

Table 3: Patients of both groups, distribution according to annual recurrence frequency of labial herpes after receiving treatment.

Table 3 compares both groups as for annual frequency of recurrence after having received corresponding treatment. When analyzing this, superiority of the group treated with laser becomes evident.

Clinical stage Time of cure
First 48 h. 3 to 4 days 5 to 7 days More than 7 days Total
Tot. % Tot. % Tot. % Tot. %
Study group(n = 116) Prodromal 26 100 0 0 0 0 0 0 26
Vesicles 40 95 2 4.8 0 0 0 0 42
Crust 31 91 3 8.8 0 0 0 0 34
Secondary infection 0 0 13 93 1 7.2 0 0 14
Control group(n=116) Prodromal 0 0 25 96 1 3.9 0 0 26
Vesicles 0 0 0 0 9 22 33 79 42
Crust 0 0 0 0 24 71 10 29 34
Secondary infection 0 0 0 0 0 0 14 100 14
Total 97 42 43 19 35 15 57 25 232

Table 4: Patients of both groups, distribution with relation to the clinical stage in which we intervened and the time of cure of the same ones.

As it can be observed in Table 4, in the study group 100 % of the prodromal stages, 95 % of the vesicular ones, and 91 % of the crust stages were able to cure during the first 48 hours. Patients with lesions infected secondarily needed more than 48 hours to cure, although they never surpassed 5 days.

These results, although astonishing, are corroborated by authors like Tunér and Schindl, where they highlight that treatment with a laser in the initial stages of Herpes Labialis has a percentage of superior success compared to conventional treatment, besides achieving an almost immediate relief of the symptoms (3, 4).

In the control group remarkable differencies are appreciated when comparing them with that of the study group. Therapy with Aciclovir in early stages (first 72 hours) has b een broadly suitable for many professionals and their use against Herpes Labialis has been studied by some authors (5).


Periods of annual recurrence in the study group were prolonged considerably after having received treatment, whilst in the control group such evident changes were not shown.

In the prodromal period the patients treated with laser all healed up in the first 48 hours, whilst those treated conventionally needed from 3 to 4 days to cure.

In the vesicular period and the period of crust, those of the study group cured in majority in the first 48 hours, whilst those of the control group needed more than 5 days.

In infected lesions those treated with laser cured mainly in 3 to 4 days, whilst those treated with medication needed more than 7 days to cure.


  1. Santana, J. C.: Altas of pathology of the buccal complex, Havana: Editorial scientific-technique, 1985:30-34
  2. Eversole, L. R.: Buccal pathology, Diagnosis and Treatment, Havana: Editorial scientific-technique, 1985:82-87
  3. Tunér, J., Hode, L.: Low Level Laser Therapy – clinical practice and scientific background, 1999, ISBN 91-630-7616-0
  4. Parker, J. et al.: The effects of laser therapy on tissue repair and pain control: a meta-analysis of literature, Proc. Third Congress WALT, Athens, Greece, May 10-13, 2000, p. 77
  5. Vélez-González, M. et al.: Treatment of relapse in herpes simplex on labial and facial areas and of primary herpes simplex on genital areas and area pudenda with low power He-Ne laser or Acyclovir administered orally, SPIE Proc. 1995, Vol. 2630:43-50
  6. Garrigó M. I., Valiant C.: Biological effects of radiation of low power laser in the repair histica, Rev. Cub. Estomat, 1996:33 (2)
  7. Simunovic, Z.: Lasers in Medicine and Dentistry, Vitagraf, Croatia, 2000.


Fig. 1: Herpes Day 1 (occurrence) Fig. 2: Herpes Day 1+ (first laser treatment)


Fig. 3: Herpes Day 2 (morning, condition after 2 treatments) Fig. 4: Herpes Day 2+ (afternoon, condition after 3 treatments)


Fig. 5: Herpes Day 3 (afternoon, cured after 4 treatments)  


J Investigative Dermatology. 1999; 113 (2): 221-223.

Low-intensity laser therapy is an effective treatment for recurrent herpes simplex infection.  Results from a randomized double-blind placebo controlled study.

Schindl A, Neuman R.

50 patients with recurrent perioral herpes simplex infections (at least once a month for more than 6 months) were treated with 690 nm, 80 mW laser, 48 J/cm2, in a double blind study. Patients received daily irradiations for two weeks, 10 treatments. The treatment was given in a recurrence-free period and the irradiation was given at the site of the original herpes simplex infection. If both lips were involved, both upper and lower lips were treated. Patients were monitored for 52 weeks. The mean recurrence-free interval in the laser group was 37.5 weeks (range; 2-52 weeks) and in the placebo group 3 weeks (range 1-20 weeks). No side effects were noted.


Kevin C Moore Naru Hira. Parswanath S. Kramer, Copparam S. Jayakumar and Toshio Oshiro

Post herpetic. neuralgia can he an extremely painful condition which in many cases proves resistant lo all the accepted forms of treatment. II is frequently most severe in the elderly and may persist for years with no predictable course.

This trial was designed as a double blind assessment of the efficacy of low level laser therapy in the relief of the pain of post herpetic neuralgia with patients acting as their own controls. Admission to the trial was limited to patients with . established post herpetic neuralgia of at least six months duration and who had shown little or no response to conventional methods of treatment. Measurements of pain intensity and distribution were noted over a period of eight treatments in two groups of patients each of which received tour consecutive laser treatments. The results ides demonstrate a significant reduction in both pain intensity and distribution following a course of low level laser therapy.


Toshikazu Hashimoto, Osamu Kemmotsu, Hiroshi Otsuka, Rie Numazawa, and
Yoshihiro Ohta,

Department of Anaesthesia, Hokkaido University Hospital, Sapporo, Japan

In the present study we evaluate the effects of laser irradiation on the
area near the stellate ganglion on regional skin temperature and pain
intensity in patients with postherpetic neuralgia. A double blind, crossover
and placebo-controlled study was designed to deny the placebo effect of
laser irradiation. Eight inpatients (male 6, female 2) receiving laser
therapy for pain attenuation were enrolled in the study after institutional
approval and informed consent. Each patient received three session s of
treatment on a separate day in a randomised fashion. Three minutes
irradiation with a 150 mW laser (session 1), 3 minutes irradiation with a 60
mW laser (session 2), and 3 minutes placebo treatment without laser
irradiation Neither the patient nor the therapist was aware which session
type was being applied until the end of the study. Regional skin temperature
was evaluated by thermography of the forehead, and pain intensity was
recorded using a visual analogue scale(VAS). Measurement were performed
before treatment, immediately after (0 minutes) then 5, 10, 15, and 30 min
after treatment. Regional skin temperature increased following both 150 mW
and 60mW laser irradiation, whereas no changes were obtained by placebo
treatment. VAS decreased following both 150 mW and 60 mW laser treatments,
but no changes in VAS were obtained by placebo treatment. These changes in
the temperature and VAS were further dependent on the energy density, i.e
the dose. Results demonstrate that laser irradiation near the stellate
ganglion produces effects similar to stellate ganglion block. Our results
clearly indicate that they are not placebo effects but true effects of laser


Photomed Laser Surg. 2014 Aug;32(8):450-457.

Low-Level Light Therapy Induces Mucosal Healing in a Murine Model of Dextran-Sodium-Sulfate Induced Colitis.

Zigmond E1, Varol C, Kaplan M, Shapira O, Melzer E.

Author information

  • 11 Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center & the Sackler Faculty of Medicine , Tel-Aviv, Israel .


Abstract Objective: The aim of this study was to demonstrate the effect of low-level light therapy (LLLT) in an acute colitis model in mice.

Background data: Low-level light therapy (LLLT) has been shown to be an effective treatment for various inflammatory processes such as oral mucositis and diabetic foot ulcers.

Methods: Colitis was induced by dextran sodium sulfate (DSS) in mice in four blinded controlled studies (validation of model, efficacy study, and two studies for evaluation of optimal dose). LLLT was applied to the colon utilizing a small diameter endoscope with an LED-based light source in several wavelengths (440, 660, and 850 nm at 1 J/cm2) and then 850 nm at several doses (1, 0.5, 0.25, and 0.1 J/cm2). LLLT was initiated 1 day prior to induction of colitis and went on for the 6 day induction period as well as for the following 3-10 days. Dose was controlled by changing exposure time. Disease activity was scored endoscopically and by histopathological assessment.

Results: Statistically significant improvement in disease severity was observed in the treatment groups compared with the control groups. The three wavelengths used demonstrated efficacy, and a clear dose-response curve was observed for one of the wavelengths (850 nm). On day 11, colonoscopic scoring in the sham-treated mice increased from 7.9±1.3 to 12.2±2.2, while activity in all treated groups remained stable.

Conclusions: Photobiostimulation with LLLT has a significant positive effect on disease progression in mice with DSS colitis.


Lasers Med Sci. 2014 May 29. [Epub ahead of print]

Near-infrared low-level laser stimulation of telocytes from human myometrium.

Campeanu RA1, Radu BM, Cretoiu SM, Banciu DD, Banciu A, Cretoiu D, Popescu LM.


  • 1Department of Anatomy Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095, Bucharest, Romania.


Telocytes (TCs) are a brand-new cell type frequently observed in the interstitial space of many organs (see ). TCs are defined by very long (tens of micrometers) and slender prolongations named telopodes. At their level, dilations-called podoms (~300 nm), alternate with podomers (80-100 nm). TCs were identified in a myometrial interstitial cell culture based on morphological criteria and by CD34 and PDGF receptor alpha (PDGFRα) immunopositivity. However, the mechanism(s) of telopodes formation and/or elongation and ramification is not known. We report here the low-level laser stimulation (LLLS) using a 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (with an output power of 60 mW) of the telopodal lateral extension (TLE) growth in cell culture. LLLS of TCs determines a higher growth rate of TLE in pregnant myometrium primary cultures (10.3 ± 1.0 μm/min) compared to nonpregnant ones (6.6 ± 0.9 μm/min). Acute exposure (30 min) of TCs from pregnant myometrium to 1 μM mibefradil, a selective inhibitor of T-type calcium channels, determines a significant reduction in the LLLS TLE growth rate (5.7 ± 0.8 μm/min) compared to LLLS per se in same type of samples. Meanwhile, chronic exposure (24 h) completely abolishes the LLLS TLE growth in both nonpregnant and pregnant myometria. The initial direction of TLE growth was modified by LLLS, the angle of deviation being more accentuated in TCs from human pregnant myometrium than in TCs from nonpregnant myometrium. In conclusion, TCs from pregnant myometrium are more susceptible of reacting to LLLS than those from nonpregnant myometrium. Therefore, some implications are emerging for low-level laser therapy (LLLT) in uterine regenerative medicine.



Brain Effects of Laser Acupuncture

Acupunct Med. Sep 2013; 31(3): 282–289.
Published online Aug 6, 2013. doi:  10.1136/acupmed-2012-010297

Differential brain effects of laser and needle acupuncture at LR8 using functional MRI

Im Quah-Smith,1 Mark A Williams,2 Thomas Lundeberg,3 Chao Suo,1 and Perminder Sachdev1

1School of Psychiatry, University of New South Wales and Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, New South Wales, Australia

2Macquarie Centre for Cognitive Sciences (MACCS), Macquarie University, North Ryde, Sydney, New South Wales, Australia
3Rehabilitation Medicine University Clinic, Danderyds Hospital AB, Stockholm, Sweden
Correspondence to Professor Perminder Sachdev, School of Psychiatry, University of New South Wales and Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Randwick, NSW 2031, Australia; ua.ude.wsnu@vedhcas.p

Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to


Acupuncture is a popular form of complementary medical intervention used to treat a number of disorders including neuropsychiatric illnesses.1–8 The traditional modality of acupuncture has been with needles applied manually. A number of investigators have examined the possible mechanisms by which needle acupuncture (NA) may produce physiological effects, with many neural structures being implicated including peripheral nerves, neurovascular bundles, mechanoreceptors, nerve endings and neuromuscular attachments.9–18

In the 1970s, with the advent of laser technology, low intensity laser acupuncture (LA) emerged as a new modality of acupuncture and increased in popularity. The main advantages of LA were that it was painless and infection-free because there was no needle puncture. It was also easy to deliver, making it time-efficient and cost-effective. Because of the lack of any skin sensation, low intensity laser was also easy to blind in any experimental design, making it an ideal research tool. In spite of these qualities and its increasing clinical importance, there is a dearth of investigations into its neurophysiological effects and clinical efficacy.19–21 Little is known about the peripheral pathways and spinal and central mechanisms involved in LA.

The application of functional MRI (fMRI) to acupuncture research has opened up an avenue to investigate the CNS effects of the various modalities of acupuncture.22–34 In our previous studies, fMRI was used to examine the brain response to LA on four acupuncture points (LR8, LR14, CV14 and HT7) in both healthy participants and those with depression.35 36 The choice of acupuncture points in the fMRI studies was based on a pilot clinical study to demonstrate the effectiveness of a suite of acupuncture points in the treatment of mild to moderate depression in primary care,8 with LR8 stimulation having produced the most salient effect. These studies showed that the brain activation patterns in depression during LA were different from those in healthy participants, with a significant shift from the frontolimbic cortices to the parieto-temporal-cerebellar regions in those with depression. Another network of interest found with the brain effects of acupuncture is the default mode network (DMN),37 38also known as the resting state network. The DMN is active when the brain is not involved in any specific task. When the DMN is active, self- referential activity occurs in the resting brain as part of its preparation before the next task.37 38 This self-referential activity is associated with the ‘sense of self’ important in the well-being of the individual.

In this study we chose LR8 (which produced the most salient antidepressant effect in our previous work) to compare the brain effects of the two modalities (LA vs NA) in healthy individuals. We also wanted to record their impact on the DMN.




Sixteen healthy individuals (eight women and eight men) aged 18–60?years (mean 48.2?years) were recruited by advertisement through the University of New South Wales, Black Dog Institute and a private medical acupuncture clinic in Sydney.

Study design

Each participant received LA on the medial knee acupuncture point LR8 (at the junction of the semitendinosus and semimembranosus tendon insertion site above the knee) and NA at LR8 on the other leg, with the side of stimulation being counterbalanced across the group; in other words, for the whole sample there was equivalent left- and right-sided stimulation with NA and LA.

During the fMRI scan, two runs were used for either LA or NA condition in randomised order. Each run had alternating rest/active phases, beginning with a rest phase, and consisted of 17 blocks with eight active phases (block) alternating with nine rest phases (block). The duration of each active block was 20 s, including 2 s preparation time, 16s of continuous acupuncture stimulation and 2 s of repetition time (TR) at the end for the scanner to pick up the BOLD signal. The rest block was set at 20 s to match the active block. Both laser stimulation and needle stimulation were time-locked to signalling.

Inclusion criteria

Participants were right-handed, had no history of significant medical or psychiatric disorder, were not currently on any medication other than vitamin supplements, had no contraindications to an MRI scan and provided written informed consent.

Exclusion criteria

Exclusion criteria included ongoing uncontrolled systemic illness, acute illness, brain injury, past surgery involving the lower limbs and any contraindications to MRI (pacemaker, ferromagnetic implants or foreign body, claustrophobia).

Withdrawal criteria

Subjects were withdrawn if any of the abovementioned exclusion criteria occurred in the interim before the procedure or if the subject became agitated or anxious during the procedure.

Randomisation and blinding

Randomisation has been described above in the study design. There was no blinding of either the participant or the acupuncturist. The block (rest/active) design accommodated for the placebo response to both needle and laser stimulation.



Practitioner background

LA and NA were conducted by IQ-S and TL. IQ-S is a Fellow of the Australian Medical Acupuncture College (AMAC) and has been a clinical acupuncturist for 20 years. TL has expertise in integrative neurophysiology and is a rehabilitation medicine specialist

The needle

Single usage Helio-sourced non-ferrous silver needles with dimensions 0.22 mm×25mm, which are compatible with the magnet, were used. The location of LR8 was confirmed by anatomical landmarks and needle puncture was followed by rotation in 1 Hz cycles in a 45 degrees clockwise direction to produce the de qi sensation typical of manual acupuncture while undergoing MRI acquisition. The needling blocks were achieved with time-lock to signalling for MRI acquisition.

The laser

A Moxla prototype fibreoptic infrared light laser (Euryphaessa AB, Stockholm, Sweden), 808 nm with 20 mW capacity and a fibreoptic arm was developed for use in the scanning room. Location was confirmed by anatomical location. A stably-held laser was applied to the skin by the acupuncturist for the duration of the laser session according to the time signal. The switching on and off was achieved with a computer signal time-locked to the MRI acquisition.

Sensory stimulation reporting

After the acupuncture intervention under fMRI acquisition the participants were each asked to assess the sensory stimulation they underwent; the sensory descriptions were light touch, pressure, fullness, heaviness, ache, soreness, numbness, tingling, warmth, pain and ‘other’



Imaging was performed on a 3T Philips Intera MRI scanner (Philips Medical Systems, Best, The Netherlands) for both T1-weighted three-dimensional (3D) structural and BOLD contrast functional MRI. The 3D structural MRI was acquired in sagittal orientation using a T1-weighted TFE sequence (TR/TE=6.39/2.9 ms; flip angle=8; matrix size=256×256; FOV=256×256 mm; slice thickness 1.0 mm), yielding sagittal slices of 1.0?mm thick and an in-plane spatial resolution of 1.0×1.0?mm, producing an isotropic voxel of 1.0×1.0×1.0?mm. A gradient echo-planar imaging (EPI) technique (TR/TE=2000/40 ms; matrix size=128×128; FOV=250×250 mm; in-plane pixel size 1.953×1.953?mm) was used to acquire T2-weighted BOLD contrast fMRI in axial orientation. The whole brain was covered using 21 slices at 5.0 mm slice thickness.

Image preprocessing

Imaging data were analysed using statistical parametric mapping (SPM2, Wellcome Department of Cognitive Neurology, London, UK) implemented in Matlab V.6 (The Mathworks). All volumes were realigned spatially to the first volume and the time series for voxels within each slice realigned temporally to acquisition of the middle slice. Resulting volumes were normalised to a standard EPI template based on the MNI. The normalised images were smoothed with an isotropic 8 mm full-width half-maximal Gaussian kernel. The time series in each voxel was highpass filtered to 1/120 Hz to remove low-frequency noise.

Image postprocessing

Statistical analysis was performed in two stages assuming a random effects design. Each stimulation site was compared with the rest condition for first-level analysis. The BOLD response to the acupuncture stimulation was modelled by a canonical haemodynamic response function (HRF).

Half the participants’ images were flipped and the group was then processed as a whole under second-level analysis (ANOVA) at the whole brain level. Each individual participant's contrast images, which were effectively the statistical parametric maps of the t-statistics for each voxel from the first-level analysis, were put into this second-level design. We used a one-sample t test to examine the activation pattern of each acupuncture group and a within-subject two-sample t test to compare the activation differences between the two types of acupuncture. To correct for multiple comparisons, areas with a p value<0.05 following cluster-level Family Wise Error (FWE) correction were considered significant, with an initial uncorrected p value threshold of <0.001 and the extent threshold to 15 contiguous voxels.



First-level analysis

NA at LR8 showed increased activation at the right insula (pFWE=0.001) and left precentral gyrus and insula (pFWE<0.001) (figure 1, table 1). There was also deactivation at the left precuneus (pFWE=0.002). No significant results were found for LA acupuncture at LR8, indicating that there was no consistent activation or deactivation at the first level.

Table 1



First-level analysis relative to resting state: significant results for NA

Figure 1



Figure 1

A one-sample t test was used to show the activation pattern of needle acupuncture. Significant activation (p<0.05) corrected (Family Wise Error) was found at the bilateral insula and left precentral gyrus as well as deactivation at the left precuneus.

Second-level analysis

When the activation patterns for LA and NA were compared, NA produced greater activation in the left precentral gyrus (pFWE=0.023) and LA produced more activation in the left precuneus (pFWE=0.003) (figure 2, table 2).

Table 2



Second-level analysis: significant activation differences between NA and LA

Figure 2




A within-subject t test was used to show differences in activation between needle acupuncture and laser acupuncture. Needle acupuncture activated the left precentral gyrus while laser acupuncture activated the left precuneus. All the results have been

Sensory stimulation: laser versus needle

All participants felt the touch of the laser probe but only a few reported any sensation produced by the laser beam itself, with three reporting a tingling sensation, one a feeling of warmth and one reporting both these sensations. Needle acupuncture with de qi produced more sensory changes, with all participants reporting pressure and tingling and three reporting pain (see online appendix, supplementary tables S1 and S2).

Adverse effects: laser and needle acupuncture, MRI experience

On a scale of 0 (none) to 6 (severe), mean scores of adverse effects with LA were: transient tiredness and dizziness (0.13), vagueness (0.125) and nausea (0.06). Adverse effects with NA were: pain (0.50) and unwell (0.13). The MRI experience caused mild discomfort (0.44) and anxiety (0.44) (see online appendix, supplementary table S3).



Functional MRI studies with NA have indicated that deactivation of the limbic-paralimbic-neocortical network and activation of the somatosensory cortex are involved during NA intervention. Deactivation of the limbic system occurs with correct de qi needling technique, whereas poor technique resulting in the pain sensation causes the opposite reaction (activation of the limbic system). Some of the limbic-paralimbic regions were identifiable as being part of the DMN.12 13 22 23 These studies have selected acupuncture points which are clinically known to be uncomfortable when de qi needling is applied (eg, LI4 and ST36). The insula is involved in NA and our first-level findings confirmed those in the literature.12 13 27–34 The limited literature on the brain effects of LA suggests limbic-paralimbic-neocortical activation but no significant activation of the somatosensory cortex.20 21 Ipsilateral brain activation was also observed. One study on healthy participants reported that this ipsilaterality was only seen with limb acupuncture points and not truncal acupuncture points.35 The ipsilaterality suggests the involvement of the autonomic nervous system in LA mechanisms of action. There was no significant activation or deactivation of the somatosensory cortex, with the low intensity laser stimulation being free of pain or ache. This may contribute to the interindividual variability in the first-level analysis with LA while first-level analysis with NA demonstrated significant activation of the insula, important in pain pathways and deactivation of the posterior DMN. Unlike previous NA studies reporting somatosensory cortical changes, the precentral gyrus linked to the primary motor cortex was activated. The above literature therefore suggests that the NA and LA acupuncture afferent pathways may be different, the former due to its somatosensory and sensorimotor input following afferent pain pathways9 10and the latter possibly more autonomically driven.19 35 36

The literature shows that both NA and LA modulate the DMN. The DMN is a composite of brain regions activated when the brain is at rest and not involved in an active task. It is therefore also referred to as the task negative brain network. During DMN time the healthy individual reflects on his or her life and his or her hopes and aspirations.39 It may be that activation of the DMN is responsible for the feeling of well-being from acupuncture intervention. Some may argue the case that the well-being is from the placebo effect. The DMN may be an integral part of every acupuncture intervention, directly contributing to the maintenance of ‘sense of self’ and well-being.3740

The posterior DMN is important in depression.40 41 LR8 is the most important acupuncture point in the LA treatment regime for depression that was tested in our previous work.35 The significant activation of the left precuneus (as part of the posterior DMN) after FWE correction when LA is applied to LR8 across the group in the second-level analysis is further confirmation of the clinical efficacy of LA in depression.8 In NA, deactivation of the left precuneus was noted at the first-level analysis, confirming the deactivation of this part of the posterior DMN. This could be part of an antidepressant effect of NA at LR8. Further needle fMRI acupuncture studies are needed to confirm the efficacy of this acupuncture point in depression.

In the first-and second-level analyses, measuring activation less than or greater than a baseline (in this case, rest) are referred to as deactivation and activation, respectively. However, in this study, for second-level analysis, deactivation is impossible to interpret as we are subtracting two tasks from each other (NA vs LA) and not comparing them with rest. We found that NA significantly stimulated the left precentral gyrus compared with LA, and the latter significantly activated the left precuneus compared with the former. It is not known why the left precentral gyrus in NA and the left precuneus in LA are stimulated for these modalities in this comparison. In the protocol it was ensured that equivalent numbers of left- and right-sided NA and LA were conducted. The left-sidedness may be limited to our sample alone. Further studies may be required to clarify the brain functions of LR8 when stimulated by different modalities of acupuncture.

Interestingly, in spite of NA at this acupuncture point using the de qi method to cause the traditional ‘achy’ sensation, there was no significant stimulation of the somatosensory cortex (represented as the post-central gyrus). Instead, NA at LR8 produced significant activation at the precentral gyrus after FWE correction. The precentral gyrus is an important region which includes the motor cortical regions42 (primary motor or somatomotor cortex and the lateral premotor cortex). Previously, sensorimotor implicated acupuncture points (GB34, GB35, GB39, ST36 on the leg and LI9, LI10, LI13, LI14 on the arm) have been shown to increase brain activation of the premotor and supplementary motor regions.43 Another study showed that NA at GB34/BL57 caused deactivation of the primary motor cortex and premotor cortex.44 The findings of NA at LR8 in this study are only preliminary fMRI evidence. More investigations are warranted to evaluate the role of NA at LR8 in the modulation of motor cortical regions and hence its likely usefulness in motor rehabilitation clinically.

Empirically, LR8 is not particularly uncomfortable or painful when needled to produce the de qi sensation, unlike widely investigated acupuncture points ST36 or LI4 which are known to be uncomfortable to similar needling. This observation suggests that maybe not all acupuncture points produce somatosensory changes when needled.12 25In the case of LR8, the outcome from this study is that NA at this acupuncture point is significantly somatomotor. In the literature, among its applications, LR8 is empirically used for muscle spasms, pareses and paretic tendencies.45 Classically, it is meant to ‘benefit the sinews’. It would be interesting to perform further work on other mid lower limb acupuncture points to test their sensorimotor implications.

The sensory signalling (if any) perceived by the participants from LA was light touch (for all participants) and tingling and/or warmth (n=2), and only one participant felt pressure. Warmth being C fibre-linked and light touch and tingling being more so, A-β linked sensations may be part of LA's afferent fibres. Evaluation of the sensory signalling with NA showed that pressure and tingling (n=10) were felt by more participants than light touch (n=6) or ache (n=5). Interestingly, with LA all of the participants felt light touch and only three participants felt anything more than light touch. This may suggest an Aβ and possibly non-nociceptive C afferent involvement with LA, whereas NA probably sets up activity in A-β, A-δ and C fibres (nociceptive as well as non-nociceptive).9 46More investigations are warranted to identify definitively the afferent fibre types involved in LA.

There are limitations to these findings. They may be confined to this low intensity laser (808?nm). Although we had 16 participants, this is still a relatively small sample size. This study was conducted on healthy participants and NA or LA at LR8 may produce totally different brain patterns in participants with health problems.



NA and LA at LR8 produce different brain patterns, highlighting the differential application of these two modalities of acupuncture. These activation patterns are consistent with the suggestion that LA at LR8 may be useful in the treatment of mood disorders while NA at LR8 may be useful in the modulation of motor cortical regions and hence may have a place in motor rehabilitation. These are only preliminary findings and further investigations with larger samples are warranted.

Summary points

  • Laser and needle acupuncture at LR8 significantly activated different brain regions.
  • Laser acupuncture activated the precuneus, part of the posterior default mode network.
  • Needle acupuncture activated the precentral gyrus, part of the motor cortical brain regions and not the sensory cortical brain regions.


Supplementary Material

Web tables:



We thank Helio Australia for supplying the MRI friendly silver needles. Thanks to all our participants for their time and contribution, to Julie-Ann Ho for their recruitment and to Kate Bromley and Beverley Stanton for their help in laser signalling.



Contributors: IQ-Sdesigned and managed the study, recruited participants, conducted the laser/needle intervention under fMRI, analysed the data and wrote the manuscript. MW helped with study design and data analysis. TL conducted the laser/needle intervention under fMRI and helped with writing the manuscript. CS analysed the data and helped with writing the manuscript. PS contributed to the study design, ethical application and writing the manuscript.

Funding: This project was funded by Thyne Reid Foundation and Louise Dobson and family. We thank them for their support.

Competing interests: None.

Ethics approval: This study was approved by the Human Research Ethics Committee, South East Health, South Eastern Illawarra Area Health Service, Sydney, Australia.

Provenance and peer review: Not commissioned; internally peer reviewed.

Data sharing statement: We are happy to discuss data sharing as approved by the senior author Professor Perminder Sachdev.



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PLoS One. 2010; 5(9): e12619.
Published online Sep 7, 2010. doi:  10.1371/journal.pone.0012619

The Brain Effects of Laser Acupuncture in Healthy Individuals: An fMRI Investigation

Im Quah-Smith,1 Perminder S. Sachdev,1,2,3,* Wei Wen,1,2,3 Xiaohua Chen,1,2,3 and Mark A. Williams4

Pedro Antonio Valdes-Sosa, Editor

1School of Psychiatry, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
2Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia
3Brain & Ageing Research Program, School of Psychiatry, University of New South Wales, Randwick, New South Wales, Australia
4Macquarie Centre for Cognitive Sciences, Macquarie University, Sydney, New South Wales, Australia
Cuban Neuroscience Center, Cuba

Conceived and designed the experiments: IQS. Performed the experiments: IQS. Analyzed the data: IQS PSS WW XC MAW. Wrote the paper: IQS PSS WW MAW. Recruited participants: IQS. Involved in design: WW XC PSS. Involved in data acquisition: XC. Involved in interpretation of results: MAW PSS.

Received March 1, 2010; Accepted August 5, 2010.

Copyright Quah-Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Despite the remarkable developments in Western Medicine in modern times, public interest in Traditional, Complementary and Alternative Medicine (TCAM), such as acupuncture, remains high [1], [2]. This may be because TCAM is perceived as holistic and relatively free of adverse effects. However, these treatments sit uncomfortably alongside scientific medicine because of strikingly different explanatory systems and the empirical tests applied by each discipline. In order to bridge the gulf between high public acceptability and the lack of empirical evidence for many of these treatments, it is important to reconcile them with modern scientific concepts. Our focus here is on laser acupuncture, and we address the question whether laser acupuncture produces brain effects that are biologically plausible.

There have been many studies [3][20] some of which have involved functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) of the brain effects of needle acupuncture. Some neuroimaging and neuroendocrine studies have suggested that needle acupuncture affects hypothalamic as well as extrahypothalamic functions and modulates mood [3], [5][9]. Needling of the leg acupoint ST36 and the hand acupoint LI4 was shown to activate the hypothalamus and nucleus accumbens and deactivate the rostral anterior cingulate cortex (rACC) [3]. Superficial needling (i.e. needling that did not produce the classical de qi sensation – tingling, numbness or other sensations that occur after an acupuncture needle has been properly placed in the body) and non-acupoints (i.e. points on the skin that do not lie on recognized meridians in Traditional Chinese Medicine [TCM]) did not activate the hypothalamus [7]. Stimulation of the acupoint PC6, located above the wrist, recommended for a wide range of conditions from nausea to stress management, resulted in activation of the cerebellum, dorsomedial nucleus of the thalamus, anterior cingulate gyrus and left superior frontal gyrus [8]. All of these studies have used needle acupuncture which, although more traditional, is invasive.

While laser acupuncture has become an increasingly common clinical method, particularly in primary care, its empirical basis has been less well studied to date. Whereas needle acupuncture studies have shown activation and deactivation of the somatosensory cortex [3], [4], [6], [7], [11][14], superficial needling and laser intervention appear to stimulate cortical and subcortical structures other than the somatosensory cortex [11], [19], [20]. This is consistent with the observation that low intensity laser stimulation does not produce a skin sensation. For example, laser acupuncture of a foot acupoint, classically used for treating visual problems, was demonstrated to cause activation of the occipital cortex [19].

This study has used laser delivered at low intensity as used in primary care. Other studies have reported high intensity lasers can produce de qi sensation [21]. High intensity laser is not commonly used in primary care situations and therefore was not used in the current study. Further, as low intensity laser does not result in sensory sensation it is ideal for double blind randomized controlled studies where the subjects could not differentiate between placebo (laser off) and verum laser (laser on).

The evidence suggests that cortical activation does occur with acupuncture and this activation may be specific to certain brain regions in relation to the site and type of stimulation [11][14]. In practice, acupoint efficacy is not specific, and one acupoint can be used for several different conditions, just as one medical condition can be managed with several acupoint locations. For instance, the antidepressant effect of laser acupuncture [22] has been attributed to a group of acupoints – CV14, LR14, LR8 and HT7 (see fig.1 for anatomical location), however there are other acupoint combinations that are also applicable for the management of depression. The neurological effects of stimulation of these acupoints CV14, LR14, HT7 and LR8 in combination have yet to be investigated.

Figure 1





Selected acupoints relevant to mood and depression.

In this study, we examined the blood oxygen level dependant (BOLD) functional magnetic resonance imaging (fMRI) response to laser simulation on the above mentioned acupoints CV14, LR14, LR8 and HT7. We chose laser acupuncture as it permits blinding of application because of the lack of a local sensation at low intensity, together with the previously mentioned increases in practical usage and limited understanding of its mechanisms. We reasoned that if laser acupuncture is altering a person's mental state a neurological effect should be observable. Further, if the effect differs dependent on the site of stimulation, then the neural locus of the activity should also differ.


Materials and Methods

Ethics Statement

The study was approved by the human research ethics committee of the South Eastern Sydney & Illawarra Area Health Service and participants provided written informed consent before participation.


The participants (n = 10) (7 women, 3 men) were healthy volunteers aged 18–50 years (mean age  = 39.8 years) who were recruited by advertisement from the staff and students of the University of New South Wales and Prince of Wales Hospital, Sydney, Australia. All participants were right-handed and had no past history of depression or other psychiatric disorder, a Beck Depression Inventory [21] score <10, no history of drug or alcohol abuse, no medication intake within 3 months of the study, and no neurological or systemic disorders. Eight were acupuncture naïve and two had had needle acupuncture more than 3 months previously and did not know what to expect from laser intervention. Any contra-indications to MRI (pacemaker, ferromagnetic implants or foreign body, claustrophobia) were exclusionary.

Choice of acupoints and control point

The acupoints were selected based on results from our previous study [22] and the TCM for mood disorders[23], [24]. These acupoints lay on the classically named liver (LR), heart (HT) and conception vessel (CV) meridians. The selected points, labelled LR8, LR14, HT7 and CV14 in TCM, are shown in Figure 1. LR8 is in the medial knee region, between the insertions of the sartorius and semitendinosus muscles. LR14 is in the vicinity of the 6th intercostal space on the mid clavicular line. HT7 is at the wrist crease, in the vicinity of the radial side of the flexor carpi ulnaris. CV14 is in the anterior midline, approximately 5 cm below the xiphisternum. A control non-acupoint was selected on the abdominal surface, midway between SP15 (four cun from the umbilicus) and ST25 (two cun from the umbilicus) away from the abdominal meridians.

fMRI design

A block design was used, with each block of 20 seconds duration during which the subject received either laser stimulation (switched ‘on’) or placebo stimulation (switched ‘off’) at one acupoint. The infra red laser was held with light touch on the skin surface by the acupuncturist. Since the laser produces no sensation, the subject was able to be kept blind to the phase of stimulation. The on-off cycle was repeated 4 times for each acupoint (LR14, LR8, CV14, HT7), with the 4 acupoints being stimulated twice in random order. The control point near ST25 was stimulated once per subject. The block design accomodated for the placebo (laser off) condition during its rest phases. In total there were nine runs per subject. The subject was told to relax and keep his/her eyes closed during the entire time in the scanner.

Laser stimulation

A MoxlaR prototype fiberoptic infra-red light laser (808 nm) with 25 mW capacity and a fiber optic arm was developed for usage in the scanning room. The laser parameters are similar to the one used in the clinical study we have based our investigation upon [22]. The acupoints were marked with a skin marking pencil prior to entry into the scanning room. A stably held laser was applied to the skin by the acupuncturist (IQ-S) who moved it from point to point according to the time signal. The switching on and off was achieved with a computer signal time-locked to the MRI acquisition.


Imaging was performed on a 3T Philips Intera MRI scanner (Philips Medical Systems, Best, Netherlands) for both T1-weighted 3D structural and BOLD contrast functional MRI. The 3D structural MRI was acquired in sagittal orientation using a T1-weighted TFE sequence (TR/TE  = 6.39/2.9 ms; flip angle  = 8; matrix size  = 256×256; FOV  = 256×256 mm; slice thickness 1.0 mm), yielding sagittal slices of 1.0 mm thick and an in-plane spatial resolution of 1.0×1.0 mm, producing an isotropic voxel of 1.0×1.0×1.0 mm. A gradient echo-planar imaging (EPI) technique (TR/TE = 2000/40 ms; matrix size  = 128×128; FOV = 250×250 mm; in plane pixel size 1.953×1.953 mm) was used to acquire T2-weighted BOLD contrast fMRI in axial orientation. The whole brain was covered using 21 slices at 5.0 mm slice thickness and 0.5 mm gap for each volume. Each session of 96 volumes were collected with the rate of 2s/volume.

Image preprocessing and statistical analysis

Imaging data were analyzed using statistical parametric mapping (SPM2, Wellcome Department of Cognitive Neurology, London, UK) implemented in Matlab version 6 (The Mathworks Inc., USA). All volumes were realigned spatially to the first volume and the time-series for voxels within each slice realigned temporally to acquisition of the middle slice. Resulting volumes were normalized to a standard EPI template based on the Montreal Neurological Institute (MNI). The normalized images were smoothed with an isotropic 8 mm full-width half-maximal Gaussian kernel. The time-series in each voxel were highpass-filtered to 1/120 Hz to remove low-frequency noise.

Statistical analysis was performed in two stages, assuming a random effects design. Each stimulation site was compared to the placebo (laser off) condition for first level analysis. The BOLD response to the laser acupuncture stimulation was modeled by a canonical hemodynamic response function (HRF). The second level analysis (ANOVA) used each individual subject's contrast images, which were effectively the statistical parametric maps of the t-statistics for each voxel. The data had a threshold of p <0.001 with a spatial extent of 15 contiguous voxels.

Post-imaging Assessment

After the scanning session, subjects rated selected items on the Spielberger State Anxiety Inventory [25] to describe their mental state during the period of the scanning. The ratings were: 1 (not at all), 2 (somewhat), 3 (moderately so) and 4 (very much so).



Group analysis

At the group level, there were significant increases (activation) in BOLD levels in some brain regions for acupoints LR14, CV14, LR8 and the control point compared to all the other points (verum laser per point > all others, p<0.001; see Table 1). Further, there were significant decreases (deactivation) in BOLD levels for acupoints LR14, LR8 and the control point compared to all the other points (all others > verum laser per point, p<0.001; see Table 1) in other brain regions.

Table 1



Significant brain activation patterns from laser acupuncture to LR14, CV14, LR8 and control point.

With LR8, activation of ipsilateral limbic cortex (cingulate gyrus) and deactivation of bilateral frontal cortices (middle frontal gyrus), (contralateral superior frontal gyrus), contralateral temporal cortex (middle temporal gyrus) and contralateral caudate occurred. Stimulation at the LR14 acupoint resulted in activation of contralateral frontal cortex (superior and middle frontal gyrii), contralateral parietal cortex (postcentral gyrus) and deactivation of contralateral cerebellum (cerebellar tonsil) and contralateral occipital cortex (precuneus). Acupoint CV14 produced activation of the left limbic cortex in the posterior cingulate and there was no significant deactivation in the grey matter. HT7 had no significant activation or deactivation. The control point (non acupoint or sham point), activated the contralateral parietal cortex (postcentral gyrus). It also deactivated the contralateral limbic cortex (parahippocampal gyrus).

Somatosensory cortex and laterality of cerebral activation and deactivation

Our study involved randomized stimulation of the 4 acupoints and a control point. Although there was activation of contralateral postcentral gyrus (primary somatosensory cortex or SSI) with LR14 and control point, none of the other acupoints showed any activation of the somatosensory cortex. The cortical and subcortical structures activated with stimulation of the limb acupoints tended to be largely ipsilateral to the side of stimulation.

All the acupoints and control point did not have deactivation at the somatosensory cortex. However they all had contralateral deactivations with the exception of LR8 that had bilateral middle frontal gyrus deactivation.

Behavioral observations

Participants did not describe anxiety or discomfort during scanning, except for one who found the headphones uncomfortable. The mean Spielberger scale ratings were on select items were: feeling calm (3.3), secure (3.3), relaxed (3.3), nervous (1.4), jittery (1.1), worried (1.1) or overexcited and rattled (1.1).



This is the first fMRI study to examine the effects of laser stimulation of a suite of acupoints found to be efficacious in a clinical condition (depression). A salient feature of this study was that four acupoints and a control non-acupoint (sham point) were stimulated in a random design. The subjects were unaware of the relative significance of different acupoints. The use of low level laser acupuncture, which does not produce a skin sensation, permitted the blinding of subjects to verum or placebo stimulation, something difficult to achieve with needle acupuncture.

The main finding of our study was that each acupoint or control point resulted in a different pattern of brain activity when contrasted against all the other acupoints or control point. The acupoints we investigated in this study were those that have been used in our previous treatment study for depression [22]. This finding suggests that although these acupoints are all used in the treatment of depression, the neural locus of this effect differs depending upon the site stimulated. The efficacy of these acupoints in the treatment of depression may vary greatly between patients and site stimulated, and our findings may shed some light on these effects [26].

The neuroanatomical basis of depression is not completely understood, however a number of studies have implicated abnormalities in certain brain regions, in particular the medial and dorsolateral prefrontal cortex, the cingulate gyrus and the so-called limbic brain regions (hippocampus, parahippocampal gyrus, amygdala, septal nuclei, insula, thalamus) and paralimbic regions (orbitofrontal cortex, anterior temporal lobe) [26][29]. There is converging evidence from drug treatment, cognitive-behavior therapy and brain stimulation techniques that antidepressant treatments work by modulating frontal-subcortical neuronal circuits. The most consistently reported finding is that antidepressant treatments lead to a normalization of activity in the dorsolateral prefrontal cortex, with additional changes in the subgenual cingulate region, the posterior cingulate, parahippocampal gyrus and insula[29]. Whether the change in prefrontal cortex is a primary event or secondary to changes in subcortical nuclei is unclear, but the relationship of treatment response to this suggests that it is biologically plausible that laser acupuncture could be an effective antidepressant treatment through its effects on the above brain regions.

The results show this combination of acupoints activating frontal cortex, limbic cortex and subcortical caudate. The trend is for ipsilateral activation suggestive of neurological circuitry outside the dorsal spinal columns and more likely to be autonomically driven [30][32]. Most of the deactivations were contralateral. Also LR14 and control point activations included primary somatosensory cortical activations (SSI). None of the deactivations involved SSI, however they did include the regions as described earlier that could collectively be called the affective cortex (the frontal, limbic and temporal cortices as well as the subcortical caudate). This combination of ipsilateral and contralateral activations and deactivations may perhaps be representative of the combined actions of both the spinal and autonomic nervous systems during laser acupuncture.

In classical acupuncture, there are primary and secondary acupoints for the treatment of any disorder. The approach to acupoint selection can be variable, with primary acupoints being considered essential and secondary acupoints additive for some patients. In our study, we cannot predict from these results whether any acupoint should be preferred over others for clinical use, even though LR8 deactivated more brain regions (middle and superior frontal gyrus, middle temporal gyrus and the subcortical caudate) than all the other points. These are results from a sample of healthy subjects. The question of whether the results would be different in a sample of clinically depressed subjects, needs to still be answered. Further studies are required to explore the relative value of different acupoints, the final test for which naturally lies in a clinical trial. It also cannot be stated from our study whether the treatment response can be achieved with stimulation at one point alone, or if multiple points are necessary.

There is conflicting evidence regarding acupoint specificity and whether that specificity is relative rather than absolute for any particular disorder [33][38]. Furthermore, it is debatable whether the clinical effects of acupuncture are restricted to stimulation on points that lie on the classical meridians in TCM. Our finding that laser stimulation of a non-acupoint produced some brain activation suggest that there is unlikely to be a completely neutral control non-acupoint, and this should prompt a re-examination of the use of sham points (in needle acupuncture studies) as control hence minimizing the true statistical effects of any acupoint [36][39]. It is also interesting that laser acupuncture in this study appeared to preferentially activate the limbic cortex ipsilaterally and deactivate the limbic cortex contralaterally. It has been suggested that laser stimulation preferentially activates unmyelinated afferent fibers that project ipsilaterally to the insula [40][42], which might also explain the differences from needle acupuncture.

This laser acupuncture fMRI study demonstrated the central effects of stimulation of a suite of acupoints found to be efficacious in treating depression in a primary care setting. The multiple acupoints each activated different groupings of frontal-limbic-striatal brain regions, suggesting some acupoint specificity but also a commonality in the regions affected. There was a trend for the limb acupoints to cause ipsilateral activation and contralateral de-activation. The results of the study suggest that laser acupuncture is a biologically plausible anti-depressant treatment. Its efficacy and the relative merits of the different proposed acupoints must be empirically examined.



The authors would like to thank Dr Ron Shnier (Radiologist) for his contribution and Ms Angie Russell for assistance with manuscript preparation and submission.



Competing Interests: The authors have declared that no competing interests exist.

Funding: The authors acknowledge financial support from Louise and Gary Dobson, James Fairfax and the Thyne Reid Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.



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12. Fang JL, Krings T, Weidemann J, Meister IG, Thron A. Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints. Neuroradiology. 2004;4:359–362.[PubMed]
13. Zhang WT, Jin Z, Cui GH, Zhang KL, Zhang L, et al. Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study. Brain Res. 2003;982:168–178. [PubMed]
14. Geng Li, Clifford RJ, Yang ES. An fMRI study of somatosensory implicated acupuncture points in stable somatosensory stroke patients. J Magn Reson Imaging. 2006;24:1018–1024. [PubMed]
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Saphenectomy Healing / Complications Prevention

Photomed Laser Surg.  2014 May 19. [Epub ahead of print]

Low-Level Laser Therapy Prevents Prodromal Signal Complications on Saphenectomy Post Myocardial Revascularization.

Pinto NC1, Pereira MH, Tomimura S, de Magalhães AC, Pomerantzeff PM, Chavantes MC.

Author information

  • 11 Cardiovascular and Thoracic Surgery Department of The Heart Institute, General Hospital, Medical School, University of São Paulo , São Paulo, SP, Brazil .


Abstract Background and objective: One of the most frequent treatments for ischemic heart disease is myocardial revascularization, often applying the saphenous vein as a coronary graft. However, postoperative complications may occur, such as saphenous dehiscence. According to the literature, low-level laser therapy (LLLT) has been used in the treatment of several inflammatory processes in patients. Recently, its uses have expanded to include LLLT preventive therapy and postoperative treatment. Despite our department's successful application of LLLT in the treatment of saphenectomy incisions, many colleagues are still uncertain as to laser theraphy's benefits. Therefore, the study's purpose was to evaluate tissue repair of prodromal surgical incisions after the administration of LLLT.

Materials and methods: The pilot study included 14 patients, divided into two groups. Both groups of patients received the traditional treatment; additionally, the Laser Group (n=7) received diode laser treatment (λ=780 nm, fluence=19 J/cm2, pulse=25 mW, time=30 sec, energy=0.75 J, irradiance=625 mW/cm2, beam spot size 0.04 cm2), which was applied on the edges of the saphenectomy incision. The Control Group (n=7) received conventional treatment exclusively.

Results: In the Laser Group: all seven patients showed significant improvement, whereas the Control Group had twice as many complications, including critical rates of incisional dehiscence.

Conclusions: LLLT was valuable in preventing prodromal complications in saphenectomy post myocardial revascularization.

Rev Bras Cir Cardiovasc. 2009 Mar;24(1):88-91.

Low level laser therapy in acute dehiscence saphenectomy: therapeutic proposal.

[Article in English, Portuguese]

Pinto NC, Pereira MH, Stolf NA, Chavantes MC.

Service of Laser Medical Center, Heart Institute – InCor/HC – Faculty of Medicine of the Universitof São Paulo, São Paulo, Brasil.

Dehiscence is a feared complication after major surgeries. Patient who had undergone coronary artery bypass grafting developed saphenectomy's dehiscence on lower limb with edema and pain on the 15th postoperative day. Conventional treatment had been initially performed without clinical improvement. On the 30th postoperative day only Low Level Laser Therapy (LLLT) was applied punctually around surgical wounds edge. The results revealed granulated tissue, reduction of inflammatory process and analgesic effect since the first application. In this pilot study, LLLT has shown a considerable role as a wound healing agent, through a new proposal for efficient, safe and noninvasive therapy.

Intracranial Photobiomodulation

J Neurosurg.  2014 Mar;120(3):670-83. doi: 10.3171/2013.9.JNS13423. Epub 2013 Oct 25.

Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice.

Moro C1, Massri NE, Torres N, Ratel D, De Jaeger X, Chabrol C, Perraut F, Bourgerette A, Berger M, Purushothuman S, Johnstone D, Stone J, Mitrofanis J,Benabid AL.
  • 1CEA-Leti, Grenoble, France; and.



Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to the brain, from inside the brain, NIr to the brain. They developed a novel internal surgical device that delivers the NIr to brain regions very close to target damaged or diseased cells. They suggest that this device will be useful in applying NIr within the large human brain, particularly if the target cells have a very deep location.


An optical fiber linked to an LED or laser device was surgically implanted into the lateral ventricle of BALB/c mice or Sprague-Dawley rats. The authors explored the feasibility of the internal device, measured the NIr signal through living tissue, looked for evidence of toxicity at doses higher than those required for neuroprotection, and confirmed the neuroprotective effect of NIr on dopaminergic cells in the substantia nigra pars compacta (SNc) in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice.


The device was stable in freely moving animals, and the NIr filled the cranial cavity. Measurements showed that the NIr intensity declined as distance from the source increased across the brain (65% per mm) but was detectable up to 10 mm away. At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr caused no observable behavioral deficits, nor was there evidence of tissue necrosis at the fiber tip, where radiation was most intense. Finally, the intracranially delivered NIr protected SNc cells against MPTP insult; there were consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr than in those that were not irradiated.


In summary, the authors showed that NIr can be applied intracranially, does not have toxic side effects, and is neuroprotective.





[PubMed – indexed for MEDLINE]

Ligament Repair

Lasers Med Sci.  2014 Apr 11. [Epub ahead of print]

Low-level laser therapy prevents degenerative morphological changes in an experimental model of anterior cruciate ligament transection in rats.

Bublitz C1, Medalha C, Oliveira P, Assis L, Milares LP, Fernandes KR, Tim CR, Vasilceac FA, Mattiello SM, Renno AC.
  • 1Department of Bioscience, Federal University of São Paulo, Av. Ana Costa, 95, Vila Mathias, Santos, SP, 11050-240, Brazil,


The aim of this study was to analyze the effects of low-level laser therapy (LLLT) on the prevention of cartilage damage after the anterior cruciate ligament transection (ACLT) in knees of rats. Thirty male rats (Wistar) were distributed into three groups (n=10 each): injured control group (CG); injured laser-treated group at 10 J/cm2 (L10), and injured laser-treated group at 50 J/cm2 (L50). Laser treatment started immediately after the surgery and it was performed for 15 sessions. An 808 nm laser, at 10 and 50 J/cm2, was used. To evaluate the effects of LLLT, the qualitative and semi-quantitative histological, morphometric, and immunohistochemistry analysis were performed. Initial signs of tissue degradation were observed in CG. Interestingly, laser-treated animals presented a better tissue organization, especially at the fluence of 10 J/cm2. Furthermore, laser phototherapy was able of modulating some of the aspects related to the degenerative process, such as the prevention of proteoglycans loss and the increase in cartilage area. However, LLLT was not able of modulating chondrocytes proliferation and the immunoexpression of markers related to inflammatory process (IL-1 and MMP-13). This study showed that 808 nm laser, at both fluences, prevented features related to the articular degenerative process in the knees of rats after ACLT.

Photomed Laser Surg. 2007 Jun;25(3):191-6

Effect of low-level laser therapy on healing of medial collateral ligament injuries in rats: an ultrastructural study.

Delbari A, Bayat M, Bayat M.

Avicenna Hospital, Tehran, Iran.

OBJECTIVE: This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would increase fibril diameter of transected medial collateral ligament (MCL) in rats.

BACKGROUND DATA: It has been shown that LLLT can increase ultimate tensile strength MCL healing.

METHODS: Thirty rats received surgical transect to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with He-Ne laser and 0.01 J/cm(2) energy fluency per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy fluency (density) per day and group 3 (sham-exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while control group received neither surgery nor LLLT. Transmission electron microscope (TEM) examination was performed on days 12 and 21 after surgery and dimension and density of ligament fibrils were measured. The data were analyzed by Student t-test and Mann-Whitney tests, respectively.

RESULTS: On day 12, the fibril dimension of group 2 and their density were higher than of groups 1 and 3.

CONCLUSION: LLLT with He-Ne laser on incised MCL in rats could not significantly increase fibril diameter and their density in comparison with sham-exposed group.

Photomed Laser Surg. 2005 Dec;23(6):556-60

Low-level laser therapy improves early healing of medial collateral ligament injuries in rats.

Bayat M, Delbari A, Almaseyeh MA, Sadeghi Y, Bayat M, Reziae F.

Cell and Molecular Biology Research Center, Medical School, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

OBJECTIVE: This study sought to investigate whether or not low-level laser therapy (LLLT) with a helium-neon laser increased biomechanical parameters of transected medial collateral ligament (MCL) in rats.

BACKGROUND DATA: It has been reported that LLLT can enhance tendon healing.

METHODS: Thirty rats received surgical transection to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with 0.01 J/cm(2) energy density per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy density per day, and group 3 (sham = exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while the control group received neither surgery nor LLLT. Biomechanical tests were performed at 12 and 21 days after surgery. The data were analyzed by one-way analysis of variance.

RESULTS: The ultimate tensile strength (UTS) of group 2 on day 12 was significantly higher than that of groups 1 and 3. Furthermore, the UTS and energy absorption of the control (uninjured) group were significantly higher than those of the other groups.

CONCLUSIONS: LLLT with a helium-neon laser is effective for the early improvement of the ultimate tensile strength of medial collateral ligament injuries.

Connect Tissue Res. 2005;46(3):125-30

Combined treatment of therapeutic laser and herbal application improves the strength of repairing ligament.

Fung DT, Ng GY, Leung MC.

Orthopaedic Rehabilitation Research and Microscopy Laboratory, Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China.

The present study investigated the effects of combined therapeutic laser and herbal medication protocols on injured medial collateral ligaments (MCLs) of rat knees. Fully 36 rats were evenly divided into 9 groups. Right MCLs of groups 1 to 6 and 8 were transected, while that of groups 7 and 9 remained intact. After surgery, group 1 was treated with 1 session of high-dosed laser; group 2 with 9 sessions of low-dosed laser; group 3 with an herbal plaster; groups 4 and 5 received combined treatments of groups 1 and ss and 2, and 3 respectively; groups 6 and 7 received only bandaging; groups 8 and 9 received placebo laser and no treatment, respectively. All MCLs were subjected to biomechanical testing at 3 weeks postsurgery. Results revealed significant differences among groups in ultimate tensile strength (UTS) and stiffness (p < 0.01). Combination of multiple low-dosed laser treatment with herbal treatment (group 5) resulted in higher UTS than either no treatment (groups 6 and 8), single high-dosed laser treatment (group 1), multiple low-dosed laser treatment (group 2), or herbal treatment (group 2) alone. We concluded that combined applications of laser and herb can enhance further biomechanical properties of repairing rat MCLs than separate applications at 3 weeks postinjury.

Photochem Photobiol. 2005 Feb 1; [Epub ahead of print]

In vivo Study of the Inflammatory Modulating Effects of Low Level Laser Therapy on in iNOS Expression Using Bioluminescence Imaging.

Moriyama Y, Moriyama EH, Blackmore K, Akens MK, Lilge L.

Ontario Cancer Institute Princess Margaret Hospital.

This study was designed to demonstrate that bioluminescence imaging (BLI) can be used as a new tool to evaluate the effects of low level laser therapy (LLLT) during in vivo inflammatory process. Here, the efficacy of LLLT in modulating inducible nitric oxide synthase (iNOS) expression using different therapeutic wavelengths was determined using transgenic animals with the luciferase gene under control of the iNOS gene expression. Thirty transgenic mice (FVB/N-Tg(iNOS-luc)Xen) were allocated randomly to one of four experimental groups treated with different wavelengths (lambda=635, 785, 808 and 905nm) or a control group (non-treated). Inflammation was induced by intra-articular injection of Zymosan A in both knee joints. Laser treatment (, 200 s, 5 was applied to the knees 15 minutes (or min) after inflammation induction. Measurements of iNOS expression were performed at various times (0, 3, 5, 7, 9 and 24h) by measuring the bioluminescence signal using a highly sensitive charge-coupled device (CCD) camera. The results showed a significant increase in BLI signals after irradiation with 635nm laser when compared to both the non-irradiated animals and the other LLLT treated groups indicating wavelength-dependence of LLLT effects on iNOS expression during the inflammatory process. Histological analysis was also performed and demonstrated the presence of fewer inflammatory cells in the synovial joints of mice irradiated with 635nm compared to non-irradiated knee joints. BLI demonstrated an action spectrum of iNOS gene expression following LLLT in vivo.

Lasers Surg Med. 2004;34(3):285-9.

Comparison of single and multiple applications of GaAlAs laser on rat medial collateral ligament repair.

Ng GY, Fung DT, Leung MC, Guo X.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.


BACKGROUND AND OBJECTIVES: To examine single versus multiple applications of the gallium aluminum arsenide (GaAlAs) laser on the healing of surgically injured medial collateral ligaments (MCLs) in rats.

STUDY DESIGN/MATERIALS AND METHODS: Sixteen rats were studied, with 12 receiving surgical transection to their right MCL and 4 receiving a sham injury. Group 1 (n = 4) received a single dose of GaAlAs laser therapy (wavelength 660 nm, average power 8.8 mW, pulse 10 kHz, dosage 31.6 J/cm(2)) directly to their MCL during surgery. Group 2 (n = 4) received 9 doses of GaAlAs laser therapy applied transcutaneously on alternate days (wavelength 660 nm, average power 8.8 mW, pulse 10 kHz, dosage 3.5 J/cm(2)). The controls (Group 3, n = 4) received one session of placebo laser at the time of surgery, with the laser equipment shut down, while the sham injured Group 4 (n = 4) received no treatment. Biomechanical tests for structural stiffness, ultimate tensile strength (UTS), and load-relaxation were done at 3 weeks after injury. The stiffness and UTS data were normalized by expressing as a percentage of the left side of each animal before statistical analysis.

RESULTS: The load-relaxation data did not show any differences between the groups (P = 0.18). The normalized stiffness levels of Groups 2 (81.08+/-11.28%) and 4 (92.66+/-13.19%) were significantly higher (P = 0.025) than that of the control Group 3 (58.99+/-15.91%). The normalized UTS of Groups 2 (81.38+/-5.68%) and 4 (90.18+/-8.82%) were also significantly higher (P = 0.012) than that of the control (64.49+/-9.26%). Although, Group 1 had higher mean stiffness and UTS values than the control, no statistically significant difference was found between these two groups.

CONCLUSIONS: Multiple laser therapy improves the normalized strength and stiffness of repairing rat MCLs at 3 weeks after injury. The multiple treatments seem to be superior to a single treatment when the cumulative dosages are comparable between the two modes of application.

Lasers Surg Med. 2003;32(4):286-93.

Effects of a therapeutic laser on the ultrastructural morphology of repairing medial collateral ligament in a rat model.

Fung DT, Ng GY, Leung MC, Tay DK.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.


BACKGROUND AND OBJECTIVES: Low energy laser therapy has been shown to enhance mechanical strength of healing medial collateral ligament (MCL) in rats. The present study investigated its effects on the ultrastructural morphology and collagen fibril profile of healing MCL in rats.

STUDY DESIGN/MATERIALS AND METHODS: Thirty-two mature male Sprague-Dawley (SD) rats were used. Twenty-four underwent surgical transection to their right MCLs and eight received only skin wound. Immediately after surgery, eight of the MCL transected rats were treated with a single dose of laser therapy at 63.2 J cm(-2), eight were treated with a single dose of laser therapy at 31.6 J cm(-2), the rest had no treatment and served as control. At 3 and 6 weeks after surgery, the MCLs were harvested and examined with electron microscopy for collagen fibril size, distribution, and alignment.

RESULTS: Significant differences (P < 0.001) were found in fibril diameters from the same anatomical site and time period among different groups. The mass-averaged diameters of the laser-treated (64.99-186.29 nm) and sham (64.74-204.34 nm) groups were larger than the control group (58.66-85.89 nm). The collagen fibrils occupied 42.55-59.78, 42.63-53.94, and 36.92-71.64% of the total cross-sectional areas in the laser-treated, control and sham groups, respectively. Mode obliquity was 0.53-0.84 among the three groups.

CONCLUSIONS: Single application of low energy laser therapy increases the collagen fibril size of healing MCLs in rats.