Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation

PLoS Negl Trop Dis. 2016 Oct 17;10(10):e0004998. doi: 10.1371/journal.pntd.0004998. eCollection 2016 Oct.

Abstract

Background: Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated.

Methodology/principal findings: Bmv (1 μg) was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT) was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.

Conclusion/significance: These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / adverse effects*
  • Animals
  • Bothrops
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / genetics
  • Hyperalgesia / metabolism
  • Hyperalgesia / therapy*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Kinins / genetics
  • Kinins / metabolism*
  • Low-Level Light Therapy*
  • Male
  • Mice
  • Neurons / drug effects*
  • Snake Bites / etiology
  • Snake Bites / genetics
  • Snake Bites / metabolism
  • Snake Bites / therapy*
  • Snake Venoms / administration & dosage
  • Snake Venoms / adverse effects*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Analgesics
  • Cytokines
  • Interleukin-6
  • Kinins
  • Snake Venoms
  • Tumor Necrosis Factor-alpha
  • Interleukin-10

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). NNA was supported by a phD fellowship from FAPESP (grant no. 2012/09710-8). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.