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bioRxiv · 10.1101/2025.05.23.655813

Amygdalar Calcitonin Gene-Related Peptide Driven Effects of Cold Sensitivity Induced by Peripheral Neuropathy in Mice

Trail, A. D.·Allen, H. N.·Nelson, T. S.·Widner, J. A.·Lewter, L.·Tack, S. H.·Kolber, B.
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Abstract

The central nucleus of the amygdala (CeA) is a critical regulator of nociception, and its role in pain modulation depends on factors such as hemispheric location, neuropeptide release, and experimental model. Calcitonin gene-related peptide (CGRP) is a potent neuropeptide modulator within the CeA. Previous research has demonstrated its CeA nociceptive role in migraine, visceral, arthritic, and inflammatory pain murine models. The contribution of CeA CGRP to neuropathic pain is unclear. This study examined the effects of CGRP and its receptor antagonist, CGRP 8-37, in the CeA on mechanical and cold sensitivity in two mouse models of neuropathic pain: chemotherapy-induced peripheral neuropathy (CIPN) mediated by paclitaxel (PTX) and injury-induced neuropathy through the spared nerve injury (SNI) model. Mechanical and cold sensitivity were measured using the hindpaw von Frey and topical acetone drop assays, respectively. Neither CGRP nor CGRP 8-37 in the CeA had any significant effect on mechanical sensitivity in either neuropathic pain model. In the SNI-treated mice, CGRP infusion into either the left or right CeA reduced cold sensitivity in the left and right SNI-treated hindpaw, while CGRP 8-37 infusion into the left or right CeA increased cold sensitivity in the right SNI-treated hindpaw only. In PTX-treated mice, CGRP infusion into the left or right CeA decreased cold sensitivity of the contralateral paw only. These results suggest that CGRP in the CeA influences pain modulation in a complex manner that depends not only on the hemisphere and injury site, but also on the underlying cause of the neuropathic condition. PERSPECTIVEThis article presents the anti-nociceptive properties of calcitonin gene-related peptide (CGRP) signaling within the central nucleus of the amygdala during neuropathic pain-like conditions in mice. This dataset can serve to guide novel drug development for treating chronic neuropathic pain conditions. HIGHLIGHTSO_LILateralization of the central nucleus of the amygdala (CeA) is pain-model dependent C_LIO_LICGRP signaling within the CeA is correlated with decreased cold sensitivity C_LIO_LIDifferent neuropathic etiologies yield differences in CGRP responsiveness C_LI

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Trail, A. D., Allen, H. N., Nelson, T. S., Widner, J. A., Lewter, L., Tack, S. H., Kolber, B.. 2025-05-28. Amygdalar Calcitonin Gene-Related Peptide Driven Effects of Cold Sensitivity Induced by Peripheral Neuropathy in Mice. https://doi.org/10.1101/2025.05.23.655813

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