Review
Subject Category: Review Article
British Journal of Pharmacology (2007) 152, 633–648; doi:10.1038/sj.bjp.0707440; published online 10 September 2007
Supraspinal modulation of pain by cannabinoids: the role of GABA and glutamate
Cannabinoid drugs cited in this review: Cannabinoid receptor agonists: 
9-THC; WIN 55,212-2; CP55,940; HU210; CB1 receptor antagonists: rimonabant (SR141716A), AM251; FAAH inhibitors: URB597, AA-5-HT, MAFP; MGL inhibitor: URB602, MAFP; anandamide transport inhibitor: AM404.
K Rea1, M Roche1 and D P Finn1
1Department of Pharmacology and Therapeutics, National University of Ireland, Galway, Ireland
Correspondence: Dr DP Finn, Department of Pharmacology and Therapeutics, National University of Ireland, University Road, Galway, Ireland. E-mail: David.Finn@Nuigalway.ie
Received 30 May 2007; Revised 17 July 2007; Accepted 25 July 2007; Published online 10 September 2007.
Abstract
Recent physiological, pharmacological and anatomical studies provide evidence that one of the main roles of the endocannabinoid system in the brain is the regulation of 
-aminobutyric acid (GABA) and glutamate release. This article aims to review this evidence in the context of its implications for pain. We first provide a brief overview of supraspinal regulation of nociception, followed by a review of the evidence that the brain's endocannabinoid system modulates nociception. We look in detail at regulation of supraspinal GABAergic and glutamatergic neurons by the endocannabinoid system and by exogenously administered cannabinoids. Finally, we review the evidence that cannabinoid-mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions.
Keywords:
pain, brain, cannabinoids, GABA, glutamate, neurotransmission, nociception
Abbreviations:
, Increase; 
, Decrease; 
, no change; 2-AG, 2 arachidonylglycerol; BLA, basolateral amygdala; CCK, cholecystokinin; FAAH, fatty acid amide hydrolase; GABA, -aminobutyric acid; GAD, glutamic acid decarboxylase; mGlu, metabotropic glutamate; PAG, periaqueductal gray; RVM, rostral ventromedial medulla
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