CGRPα within the Trpv1-Cre population contributes to visceral nociception
| Autor: | David C. Morris, Jon E. T. Jakobsson, Garreth Kestell, Simon J. H. Brookes, Elín Ingibjörg Magnúsdóttir, Malin C. Lagerström, Bao Nan Chen, Nick J. Spencer |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Nociception 0301 basic medicine Hot Temperature Subfamily Sensory Receptor Cells Physiology Calcitonin Gene-Related Peptide Population TRPV1 TRPV Cation Channels Neuropeptide Motor Activity Calcitonin gene-related peptide Biology Nociceptive Pain 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Ganglia Spinal Physiology (medical) Reaction Time Animals education Acetic Acid Mice Knockout education.field_of_study Behavior Animal Integrases Hepatology Gastroenterology Visceral Pain Anatomy Cell biology Disease Models Animal 030104 developmental biology Calcitonin 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 314:G188-G200 |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | 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 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%, ip) 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 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. CGRPα-mCherrylx/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 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 with 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. 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 CGRPα specifically in these neurons is unknown in pain processing from visceral and somatic afferents. We used cre-lox recombination to conditionally delete CGRPα from TRPV1-expressing neurons in mice. We show that CGRPα from within TRPV1-cre population plays an important role in visceral nociception but less so in somatic nociception. |
| Databáze: | OpenAIRE |
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