Evaluation of Cav 2.2 and Cav±2´ subunits regulation and the involvement of opioid receptors in neuronal hypersensitivity and hyperexcitability of experimental Herpetic and Post-Herpetic Neuralgia

• Grant number: 20/12120-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Camila Squarzoni Dale
• Grantee: Heloísa Alonso Matielo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Herpetic (HN) and Post-Herpetic (PHN) Neuralgia constitute herpes zoster pain, presenting as burning spontaneous pain, allodynia and hyperalgesia. Although the literature indicates inflammatory and neuropathic processes as possible causes for HN and PHN, the mechanisms described are still innacurate and animal models do not completely describe central and peripheral sensitization in nervous system. Gabapentinoids, blockers of Cav±2´ subunits in high-activated voltage gated calcium channels are first line therapy, suggesting such channels as potential targets for pain regulation. Herein, we aim to evaluate the hypersensitivity and regulation of Cav2.2 channels, and Cav±2´ subunits in DRG, sciatic nerve and spinal cord of HN-mice. We also aim to assess the pain phenotype in patients with HN and PHN and its correlation with the profile of skin small fibers and Cav2.2 channels. For that, C57BL/6 mice infected with herpes simplex virus will be assessed for mechanical hypersensitivity by Von Frey filaments and pharmacological treatment with ziconotide, pregabalin and naloxone, Cav2.2 blocker, Cav±2´ subunit ligands and opioid receptor antagonist, respectively, will be performed to evaluate their influence on hipersensitivity, Expression of channels will be assessed by western blotting and RT-PCR. The influence of Cav2.2 and MOR receptors on neuronal excitability will be investigated by electrophysiology in ND7/23 cells. Patients with HN and PHN will be evaluated using standardized pain questionnaires, and a skin biopsy will be collected for immunofluorescence of small peripheral fibers and Cav2.2. This project will allow to understand the mechanisms associated with HP and PHN, expanding treatment possibilities. (AU)