[Epub ahead of print]
Impaired endocannabinoid signalling in the rostroventromedial medulla underpins genotype-dependent hyper-responsivity to noxious stimuli.
Source
Pharmacology and Therapeutics, University Road, National University of, Ireland, Galway, Ireland; NCBES, Neuroscience Cluster and Centre for Pain Research, University Road, National University of, Ireland, Galway, Ireland.
Abstract
Pain is both a sensory and an emotional experience and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar-Kyoto (WKY) rat exhibits a stress-hyperresponsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation ofendocannabinoids and transcription of their synthesising enzymes in the rostroventromedial medulla (RVM). Pharmacological blockade of the CB1 receptor potentiates the hyperalgesia in WKY rats, while inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.
Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
KEYWORDS:
Affect, Anandamide, Cannabinoid1 (CB(1)) receptor, Fatty acid amide hydrolase (FAAH), Formalin, Pain, Rostroventromedial medulla (RVM), Wistar-Kyoto rat
- PMID:
- 24076311
- [PubMed – as supplied by publisher]
