TRPV1-MEDIATED CALCIUM OVERLOAD TRIGGERS MITOCHONDRIAL DYSFUNCTION AND NEURONAL APOPTOSIS IN NEUROPATHIC PAIN

Neuropathic pain is a prevalent and debilitating condition characterized by persistent sensory hypersensitivity and neuronal damage within peripheral and central nociceptive pathways. Increasing evidence implicates the transient receptor potential vanilloid-1 (TRPV1) channel, a highly calcium-permeable non-selective cation channel, in the development and maintenance of neuropathic pain. Here, we investigated the potential role of TRPV1 activation in driving mitochondrial dysfunction and neuronal apoptosis following peripheral nerve injury. Using a rat sciatic nerve crush model combined with targeted intrathecal pharmacological modulation, we assessed pain-related behaviors alongside mitochondrial, molecular, and cellular outcomes in the dorsal root ganglion and spinal cord. Preliminary data indicate that TRPV1 activation by capsaicin is associated with increased mechanical and thermal hypersensitivity, elevated intracellular calcium levels, impaired mitochondrial respiration, reduced ATP-linked oxidative phosphorylation, and loss of mitochondrial membrane potential. These changes were accompanied by markers consistent with mitochondrial permeability transition and activation of apoptotic pathways. In contrast, pharmacological inhibition of TRPV1 using the selective antagonist AMG9810 attenuated pain hypersensitivity and partially preserved mitochondrial function. Moreover, modulation of mitochondrial permeability transition reduced indices of neuronal apoptosis, suggesting mitochondria as a key downstream target of TRPV1 signaling. Collectively, these findings suggest that TRPV1-mediated calcium dysregulation may contribute to mitochondrial stress and neuronal vulnerability in neuropathic pain.