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CGRP alpha within the Trpv1-Cre population contributes to visceral nociception
Flinders Univ South Australia, Sch Med, Discipline Human Physiol, Adelaide, SA, Australia.;Flinders Univ South Australia, Sch Med, Ctr Neurosci, Adelaide, SA, Australia..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Flinders Univ South Australia, Sch Med, Discipline Human Physiol, Adelaide, SA, Australia.;Flinders Univ South Australia, Sch Med, Ctr Neurosci, Adelaide, SA, Australia..
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2018 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 314, no 2, p. G188-G200Article in journal (Refereed) Published
Abstract [en]

The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRP alpha 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 CGRP alpha 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 CGRP alpha-mCherry(lx/lx); Trpv1-Cre mice, the duration of immobility was significantly less than controls, and the distance CGRP alpha-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. CGRP alpha-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 CGRP alpha-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 CGRP alpha- 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 CGRP alpha specifically in these neurons is unknown in pain processing from visceral and somatic afferents. We used cre-lox recombination to conditionally delete CGRP alpha from TRPV1-expressing neurons in mice. We show that CGRP alpha from within TRPV1-cre population plays an important role in visceral nociception but less so in somatic nociception.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC , 2018. Vol. 314, no 2, p. G188-G200
Keywords [en]
calcitonin gene-related peptide, nociception, pain, transient receptor potential cation channel subfamily V member 1, visceral
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-349363DOI: 10.1152/ajpgi.00188.2017ISI: 000425923800005PubMedID: 28971837OAI: oai:DiVA.org:uu-349363DiVA, id: diva2:1201512
Funder
Swedish Research CouncilRagnar Söderbergs stiftelseÅke Wiberg FoundationAvailable from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-04-26Bibliographically approved

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Magnúsdóttir, Elín IngibjörgLagerström, Malin C.

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Developmental GeneticsDepartment of Neuroscience
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