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Publication : CGRPα within the Trpv1-Cre population contributes to visceral nociception.

First Author  Spencer NJ Year  2018
Journal  Am J Physiol Gastrointest Liver Physiol Volume  314
Issue  2 Pages  G188-G200
PubMed ID  28971837 Mgi Jnum  J:270563
Mgi Id  MGI:6276731 Doi  10.1152/ajpgi.00188.2017
Citation  Spencer NJ, et al. (2018) CGRPalpha within the Trpv1-Cre population contributes to visceral nociception. Am J Physiol Gastrointest Liver Physiol 314(2):G188-G200
abstractText  The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPalpha is highly expressed in sensory neurons of dorsal root ganglia 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 CGRPalpha from the Trpv1-Cre population using the Cre/lox system. In control mice, acetic acid injection (0.6%, ip) caused significant immobility (time stationary), an established indicator of visceral pain. In CGRPalpha-mCherry(lx/lx);Trpv1-Cre mice, the duration of immobility was significantly less than controls, and the distance CGRPalpha-mCherry(lx/lx);Trpv1-Cre mice traveled over 20 min 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. CGRPalpha-mCherry(lx/lx);Trpv1-Cre mice developed more pronounced inflammation-induced heat hypersensitivity above baseline values compared with controls. However, analyses of noxious acute heat or cold transmission revealed no difference between genotypes. Also, odor avoidance test, odor preference test, and buried food test for olfaction revealed no differences between genotypes. Our findings suggest that CGRPalpha-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 with writhing reflexes, abdominal licks, or forepaw wipes of the cheek that were unaffected by deletion of CGRPalpha- from Trpv1-Cre population and likely utilize different mechanisms. NEW & NOTEWORTHY The neuropeptide calcitonin gene-related peptide (CGRP) is highly colocalized with transient receptor potential cation channel subfamily V member 1 (TRPV1)-expressing primary afferent neurons, but the functional role of CGRPalpha specifically in these neurons is unknown in pain processing from visceral and somatic afferents. We used cre-lox recombination to conditionally delete CGRPalpha from TRPV1-expressing neurons in mice. We show that CGRPalpha from within TRPV1-cre population plays an important role in visceral nociception but less so in somatic nociception.
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