• Kieran Rea, Brendan Harhen, Bright N Okine, Manish K Madasu, Iseult C McGuire, and Kathleen Coyle.
• Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland; NCBES Galway Neuroscience Centre and Centre for Pain Research, National University of Ireland, Galway, Ireland.
• Pain. 2014 Jan 1;155(1):69-79.

AbstractPain 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 Cannabinoid1 (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.Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

41 keywords...

hide…