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Chronic pain is a serious and debilitating condition that affects one in five people around the world. In order to address this public health problem, we performed studies to elucidate the role of Cav3.3 T-type voltage-gated calcium channels in the FRICT-ION model of trigeminal (TG) neuropathic pain. Western blot and immunohistochemical analyses of TG revealed protein upregulation of Cav3.3 compared to controls. Intraperitoneal injection of a highly selective TAT-based Cav3.3 blocking peptide (TAT-C3P) in FRICT-ION mice elicited a significant reduction of allodynia that correlated with a reduction of TG Cav3.3. These data suggest that a blockade of Cav3.3 may be more effective in attenuating TG neuropathic pain in female than male mice. We aim to explore any sex differences. Finally, we studied the mechanism by which TAT-C3P affects TG neurons compared to controls using whole-cell patch-clamp electrophysiology studies of TG neurons from FRICT-ION mice at 3-4 weeks post-injury. We found that there is an electrophysiological correlation to the in vivo behavioral studies since treated TG neurons from females exhibit a significant reduction in resting membrane potential whereas those from males did not. TAT-C3P-treated TG neurons exhibited a reduction in the incidence of neurons exhibiting spontaneous activity (SA) in both males and females compared to controls. Metrics indicating health of the cell such as rheobase, input resistance, and AP half-width were not found to be significant. Therefore, blocking Cav3.3 function may be an effective strategy for the treatment of TG neuropathic pain.


Poster presented at the Brain & Behavioral Health Research Day 2021



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