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

Abstract

BackgroundEnvenoming 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 FindingsBmv (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/SignificanceThese 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.

Efeitos Do Laser De Baixa Potência Na Remissão De Feridas Causadas Pela Psoríase Vulgar

“…Leva à diminuição na apoptose dos queratinócitos, contribuindo, desta maneira para a epiderme hiperproliferativa (GOLMIA; MArTINS; SCHEINBErG, 2013). O laser de baixa potência tem se mostrado efetivo em reduzir experimentalmente níveis de TNF-α, em casos como trauma muscular (ALMEIDA et al, 2013), tenotomia parcial (GUErrA et al, 2016); injeção de veneno de cobra intraplantar (NADUr-ANDrADE et al, 2016), inflamação pulmonar por formaldeído (SILVA et al, 2015).…”

“…Asawanonda et al (2000) demonstram vantagens do tratamento, por ser um método rápido e não doloroso, em pacientes com lesões nos cotovelos e joelhos. resultados corroborados por Novák et al (2002), que trataram 48 feridas em 21 pacientes, com resultados positivos nos aspectos: vermelhidão, rigidez e descamação.…”

“…Por se tratar de um problema crônico, que necessita de uso prolongado de medicações, desenvolvese um mecanismo no qual passa a não responder à medicação. Sendo utilizados fitoterápicos (NAGAR et al, 2016), imunossupressores (EL-GHARABAWY; AHMED; AL-NAJJAR, 2017;GOLMIA;MARTINS;SCHEINBERG, 2013;SCHEINBErG, 2015) até fototerapia. Nesta forma de terapia se utiliza a radiação ultravioleta "B" e também a "A" associada com psoralênicos (PUVA), contudo além de falta de praticidade, ambas apresentam efeitos colaterais e contraindicações, principalmente para o segundo caso (DUArTE et al, 2009).…”

The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming

“…When tested on a myoblast/myotube cell culture, LLL reduced snake venom cytotoxicity and increased myoblast differentiation into myotubes [ 216 ]. The mechanisms of inhibition of venom-induced hyperalgesia have been also investigated [ 217 ]. Photobiomodulation reversed venom-induced mechanical hyperalgesia and allodynia and decreased venom-induced Fos expression, as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors.…”

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

“…Local damage induced by SBE, particularly myonecrosis, is currently a worldwide unsolved and neglected medical problem. Recently proposed therapies, such as anti-inflammatory treatment for general local effects ( 26 ) or photobiomodulation (PBM) by low-level laser therapy for the sensory effects ( 27 ), are still insufficient, showing no significant advantage on SMR. However, PBM with light emitting diode (LED) in red and infrared wavelengths showed to be a more promising therapy, since it could reduce the extent of myotoxicity, edema, inflammatory infiltrate, and hyperalgesia in mice after SBE ( 28 ).…”