Abstract
Neuropathic pain affects approximately 16 million people and, despite its great social and personal impact, currently available treatments are inadequate and have limiting side effects, including the risk of abuse. There is an urgent need to find new, effective, and safe approaches to treating neuropathic pain, as well as understanding the biological effects underlying non-pharmacological complementary approaches to chronic pain. Photobiomodulation therapy (PBMT) is an important non-opioid and non-pharmacological treatment that has been shown to be effective in inhibiting neuropathic pain. However, there is still much to be understood about how PBMT treatment suppresses pain at peripheral and central levels. Yet, most preclinical studies on pain are performed exclusively in male rodent models, ignoring one of the largest sexual disparities. This project aims to use innovative approaches to better understand how photobiomodulation therapy works to prevent and/or reduce sensitivity to pain in male and female animals. Through this study, it will be determined whether PBMT is capable of preventing and/or reversing neuropathic pain in male and female rats and mice through the use of therapy before the onset of the injury and/or after the injury has already occurred. Furthermore, possible effects of glial cells will be evaluated, through the depletion of microglia and evaluation of their different mediators after photobiomodulation treatment both preventively and reversely, both at the central and peripheral level. It is also known that the therapeutic effects of PBMT are related to positive actions on mitochondrial function, through cytochrome c oxidase. Therefore, in this study, it will be analyzed, at a peripheral level, through the analysis of the sciatic nerve and the muscle adjacent to the injury, whether PBMT interferes with the production of adenosine triphosphate (ATP), changes in oxygen consumption, and mitochondrial membrane potential. (MMP), in addition to evaluating the accumulation of reactive oxygen species (ROS). The structure of myelin in the animals' sciatic nerve will also be observed through histology, as well as the expression pattern of genes related to mitochondrial activity signaling pathways using RNA interference (RNAi). In order to observe a possible central effect of the treatment, we will evaluate the expression of the Rac1/PAK1 pathway, through the use of specific inhibitors, in order to understand a possible effect of PBMT on the expression of dendrites and the functioning of synapses. This will provide us with new insights into the molecular pathophysiology of neuropathic pain and enable innovative studies of non-pharmacological approaches to pain management. (AU)
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