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

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• 作者：Kieran Rea ; Weredeselam M. Olango ; Bright N. Okine ; Manish K. Madasu ; Iseult C. McGuire ; Kathleen Coyle ; Brendan Harhen ; Michelle Roche ; David P. Finn
• 关键词：Pain ; Affect ; Wistar&ndash ; Kyoto rat ; Cannabinoid1 (CB1) receptor ; Anandamide ; Fatty acid amide hydrolase (FAAH) ; Formalin ; Rostroventromedial medulla (RVM)
• 刊名：Pain
• 出版年：January, 2014
• 年：2014
• 卷：155
• 期：1
• 页码：69-79
• 全文大小：777 K

文摘

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 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.