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Analgesic effect of photobiomodulation on Bothrops moojeni venom-induced hyperalgesia: a mechanism dependent on neuronal inhibition and cytokines and kinin receptors modulation

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 ¼g) was injected via intraplantar in the right paw of mice. Mechanical hyperalgesia and allodynia were evaluate by von Frey filaments and was observed 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. Imunohistochemistry determine the expression of spinal cord dorsal horn of Fos protein. Real time-PCR was performed to measure messenger RNA (mRNA) expression of IL-6, TNF-±, IL-10 and kinin receptors B1 and B2 at 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia. Bmv also enhanced Fos expression, a marker of nociceptor activation, and this effect was inhibited by LLLT. An increase on mRNA levels of IL-6 and TNF-± and a decrease on IL-10 were observed upon intraplantar injection of Bmv. These effects were also reversed after LLLT. In addition, LLLT caused a significantly reduction in Bmv-induced increase of both B1 and B2 kinin receptors. 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. (AU)