Evaluation of Cav 2.2 and Cava2d subunits regulagtion and the involvement of opioid receptors in hypersensitivity and neuronal hyperexcitability of experimental herpetic and post-herpetic neuralgia

• Grant number: 20/15943-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Camila Squarzoni Dale
• Grantee: Camila Squarzoni Dale
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Cláudio Romero Farias Marinho ; Gerald W. Zamponi ; José Pinhata Otoch ; Thiago Mattar Cunha

Abstract

Herpetic (HN) and postherpetic (PHN) neuralgia characterize herpes zoster pain, as burning, spontaneous pain, allodynia, and hyperalgesia. Although the literature indicates inflammatory and neuropathic processes as causes, the mechanisms described are still imprecise, and animal models for the study of HP and PHN are incomplete regarding central and peripheral sensitization in the nervous system. We aim to evaluate the hypersensitivity and regulation of Cav2.2 channels, and Cav±2´ subunits in the DRG, sciatic nerve and spinal cord in a mouse NH model, in addition to evaluating pain in patients with HN and PHN and its correlation with the profile inflammation and the effect of photobiomodulation on your pain picture. C57BL/6 mice will be infected with herpes simplex virus and Von Frey filament mechanical hypersensitivity will be evaluated. Pharmacological treatment will be performed with ziconotide, pregabalin and naloxone, Cav2.2 blocker, Cav±2´ subunit ligand and opioid receptor antagonist, respectively; as well as evaluation of their expression by western blotting and RT-PCR. The influence of Cav2.2 and MOR receptors on cell excitability will be done by electrophysiology in ND7/23 cells. Patients with HN and PHN will be evaluated by pain and quality of life screening questionnaires, and the exteroceptive sensitivity of response to thermal and mechanical stimuli will be assessed by quantitative sensory testing (QST). Blood samples will also be collected from patients to obtain plasma and assess the levels of IL-6 in plasma by ELISA and treatment with low-intensity laser (LIB-660nm) will be carried out twice a week for 8 weeks (total of 16 sessions). This project will allow us to understand the mechanisms of HN and PHN, expanding treatment possibilities, in addition to suggesting a new adjuvant non-pharmacological therapeutic approach based on LLLT in the treatment of HN and PHN. Initial results show the hypersensitivity developed in the HN mouse model, in addition to demonstrating the antinociceptive effect of pregabalin, but not ziconotide in the model. (AU)