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    CGRPα within the Trpv1-Cre population contributes to visceral nociception.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 28:ajpgi.00188.2017. Epub 2017 Sep 28.
    University of Uppsala.
    The role of Calcitonin Gene Related Peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia (DRG) and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system. In control mice, acetic acid injection (0.6%,i.p.) caused significant immobility (time stationary) - an established indicator of visceral pain. In CGRPα-mCherrylx/lx;Trpv1-Cre mice the duration of immobility was significantly less than controls and the distance CGRPα-mCherrylx/lx;Trpv1-Cre mice travelled over 20 minutes following acetic acid was significantly greater than controls. However, following acetic acid injection, there was no difference between genotypes in the writhing reflex, number of abdominal licks, or forepaw wipes of the cheek. CGRPα-mCherrylx/lx;Trpv1-Cre mice developed more pronounced inflammation-induced heat hypersensitivity above baseline values, compared to controls. However, analyses of noxious acute heat or cold transmission revealed no difference between genotypes. Also, odour avoidance test, odour preference test and buried food test for olfaction revealed no differences between genotypes. Our findings suggest that CGRPα-mediated transmission within the Trpv1-Cre population plays a significant role in visceral nociceptive pathways underlying voluntary movement. Monitoring changes in movement over time is a sensitive parameter to identify differences in visceral nociception, compared to writhing reflexes, abdominal licks, or forepaw wipes of the cheek that were unaffected by deletion of CGRPα- from Trpv1-Cre population and likely utilize different mechanisms.

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