NEUROPROTECTIVE AND NEUROREGENERATIVE PROPERTIES OF DIRECT TRPV1 RECEPTOR AGONIST CAPSAICIN ON DORSAL ROOT GANGLIA

Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barre syndrome(GBS) are disorders characterized by sensory and motor deficits resulting from immune-mediated neuronal injury and oxidative stress. Transient Receptor Potential Vanilloid subfamily member 1 (TRPV1) mediates diverse biological effects, including anti-inflammatory and anti-oxidative effects across different cell types, when activated by its direct agonist, capsaicin. However, its role in dorsal root ganglia (DRG) neurons, key tissue affected in CIDP, remains unclear, particularly regarding neuronal survival and oxidative stress. In this study, we investigated the effects of capsaicin on DRG neurons in an in vitro setting. We first examined TRPV1 expression in DRG as well as in DRG cultures of Sprague Dawley rats and assessed the effects of varying concentrations of capsaicin on axonal growth. We then evaluated capsaicin’s influence on neurite outgrowth before and after oxidative stress induced by S-nitroso-N-acetyl-DL-penicillamine (SNAP), as well as its impact on gene expression patterns. TRPV1-dependent effects were confirmed using the TRPV1 antagonist capsazepine. Capsaicin conferred neuroprotection in DRG by enhancing neurite length and upregulating cytoprotective elements including Nuclear factor erythroid 2–related factor 2(Nrf2), Hemeoxygenase-1(HO-1), NAD(P)H:Quinone Oxidoreductase 1(NQO1) under naïve conditions, and catalase under SNAP-induced oxidative stress via TRPV1 activation. Additionally, capsaicin promoted regeneration of SNAP-damaged DRG neurons by improving neurite outgrowth through the upregulation of Growth Associated Protein 43(Gap43), Activating Transcription Factor 3(ATF3) and c-Jun, a transcription activator for neuronal repair pathways. Capsazepine abolished these protective effects, confirming a TRPV1-mediated mechanism. These findings highlight TRPV1 activation by capsaicin as a potential therapeutic strategy for CIDP.