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Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins genotype-dependent hyper-responsivity to noxious stimuli

Rea, Kieran
; 
Olango, Weredeselam M.
; 
Okine, Bright N.
; 
Madasu, Manish K.
; 
McGuire, Iseult C.
; 
Coyle, Kathleen
; 
Harhen, Brendan
; 
Roche, Michelle
; 
Finn, David P.
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Publication Date
2014-01
Keywords
ACID AMIDE HYDROLASE, FEAR-CONDITIONED ANALGESIA, CANNABINOID RECEPTOR AGONIST, STRESS-INDUCED ANALGESIA, FAAH INHIBITOR URB597, HIGH-ANXIETY RATS, BRAIN-STEM, MOLECULAR CHARACTERIZATION, BASOLATERAL AMYGDALA, INFLAMMATORY PAIN
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Rea, Kieran, Olango, Weredeselam M., Okine, Bright N., Madasu, Manish K., McGuire, Iseult C., Coyle, Kathleen, Harhen, Brendan, Roche, Michelle, Finn, David P. (2014). Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins genotype-dependent hyper-responsivity to noxious stimuli. PAIN, 155(1), 69-79. doi:10.1016/j.pain.2013.09.012
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-hyper-responsive 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 of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid(1) (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas 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. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Funder
Science Foundation Ireland
Publisher
International Association for the Study of Pain
Publisher DOI
10.1016/j.pain.2013.09.012
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Pharmacology & Therapeutics (Scholarly Articles)