Exploring Pain Management: Evaluation of Molecular, Physical, and Biochemical Mechanisms in Response to Photobiomodulation in a Model of Peripheral Neuropathy.

• Grant number: 25/08458-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Marucia Chacur
• Grantee: Matias Cardoso Grande
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/08212-6 - Exploring pain management: evaluation of molecular, physical and biochemical mechanisms in response to photobiomodulation in a model of peripheral neuropathy, AP.TEM
• Associated scholarship(s): 25/15504-1 - Physical activity and stress resilience: investigating the role of DLS-DRN pathway in stress response in female rats, BE.EP.IC

Abstract

Neuropathic pain affects an estimated 16 million people and, despite its significant 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 the treatment of neuropathic pain, as well as to understand the underlying biological effects of complementary non-pharmacological 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, much remains to be understood about how PBMT treatment suppresses pain at the peripheral and central levels. Furthermore, most preclinical studies on pain are performed exclusively in male rodent models, ignoring one of the largest sex disparities. This project aims to use innovative approaches to better understand how photobiomodulation therapy works to prevent and/or reduce pain sensitivity in male and female animals. This study will determine 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 injury and/or after the injury has already occurred. In addition, 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 in reverse, at both the central and peripheral levels. It is also known that the therapeutic effects of PBMT are related to positive actions on mitochondrial function, through cytochrome c oxidase. Therefore, this study will analyze, at the 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), in the alteration of oxygen consumption, in the mitochondrial membrane potential (MMP), in addition to evaluating the accumulation of reactive oxygen species (ROS). The structure of myelin in the sciatic nerve of these animals 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 synapse functioning. This will provide us with new insights into the molecular pathophysiology of neuropathic pain and will allow innovative studies of non-pharmacological approaches to pain control.