Molecular Neurobiology

, Volume 55, Issue 7, pp 5580–5593 | Cite as

Photobiomodulation Therapy Improves Acute Inflammatory Response in Mice: the Role of Cannabinoid Receptors/ATP-Sensitive K+ Channel/p38-MAPK Signalling Pathway

  • Laís M. S. Neves
  • Elaine C. D. Gonçalves
  • Juliana Cavalli
  • Graziela Vieira
  • Larissa R. Laurindo
  • Róli R. Simões
  • Igor S. Coelho
  • Adair R. S. Santos
  • Alexandre M. Marcolino
  • Maíra Cola
  • Rafael C. DutraEmail author


Although photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM. Here, we reported that PBM (660 nm, 30 mW, 0.06 cm2, 50 J/cm2, plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors. The use of CB1 antagonist AM281 or CB2 antagonist AM630 significantly reversed the anti-inflammatory effect of PBM. Analysis of signalling pathway downstream of cannabinoid receptors activation reveals that anti-inflammatory effects of PBM depend, in great extent, on its ability to activate ATP-dependent K+ channels and p38 mitogen-activated protein kinase. Moreover, PBM therapy significantly reduced the levels of pro-inflammatory cytokine IL-6 in both paw and spinal cord, and restored the reduction of the level of anti-inflammatory cytokine IL-10 in spinal cord after carrageenan injection. Unlike the potent cannabinoid receptor agonist (WIN 55212-2), PBM did not exert any CNS-mediated effects in the tetrad assay. Finally, PBM does not reduce inflammation and noxious thermal response induced by LPS and zymosan, a TLR4 and TLR2/dectin-1 ligand, respectively. Thus, cannabinoid receptors and, possibly, the endocannabinoid system, represent an important site of action of PBM that opens the possibility of complementary and nonpsychotropic therapeutic interventions in clinical practice.

Graphical Abstract


Phototherapy Laser Inflammation Cannabinoid receptors 



We acknowledge grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC), Programa INCT-INOVAMED (grant 465430/2014-7), Programa de Pós-Graduação em Neurociências (PGN), and Universidade Federal de Santa Catarina (UFSC), all from Brazil. E.C.D.G. and I.S.C. are MSc and PhD students in neuroscience receiving grants from FAPESC. R.R.S. holds a postdoctoral fellowship from CNPq. A.R.S.S and R.C.D. are recipient of a research productivity fellowship from the CNPq.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Laís M. S. Neves
    • 1
    • 2
  • Elaine C. D. Gonçalves
    • 1
    • 3
  • Juliana Cavalli
    • 1
  • Graziela Vieira
    • 1
  • Larissa R. Laurindo
    • 1
  • Róli R. Simões
    • 4
  • Igor S. Coelho
    • 3
    • 4
  • Adair R. S. Santos
    • 3
    • 4
  • Alexandre M. Marcolino
    • 2
  • Maíra Cola
    • 1
  • Rafael C. Dutra
    • 1
    • 3
    Email author
  1. 1.Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Center AraranguáUniversidade Federal de Santa CatarinaAraranguáBrazil
  2. 2.Laboratory of Assessment and Rehabilitation of the Locomotor Apparatus, Department of Health Sciences, Center AraranguáUniversidade Federal de Santa CatarinaAraranguáBrazil
  3. 3.Post-Graduate Program of Neuroscience, Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  4. 4.Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisBrazil

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