¹School of Biomedical Sciences, Institute of Neuroscience, Queens Medical Centre, Nottingham, UK

Correspondence: Dr MD Jhaveri, School of Biomedical Sciences, Institute of Neuroscience, University of Nottingham, E-floor, Queens Medical Centre, Nottingham, Nottinghamshire, UK. E-mail: maulik.jhaveri@nottingham.ac.uk

²These authors contributed equally to this review.

Received 25 May 2007; Revised 23 July 2007; Accepted 25 July 2007; Published online 20 August 2007.

Abstract

Cannabinoid CB₁ and CB₂ receptors are located at key sites involved in the relaying and processing of noxious inputs. Both CB₁ and CB₂ receptor agonists have analgesic effects in a range of models of inflammatory and neuropathic pain. Importantly, clinical trials of cannabis-based medicines indicate that the pre-clinical effects of cannabinoid agonists may translate into therapeutic potential in humans. One of the areas of concern with this pharmacological approach is that CB₁ receptors have a widespread distribution in the brain and that global activation of CB₁ receptors is associated with adverse side effects. Studies of the endogenous cannabinoids (endocannabinoids) have demonstrated that they are present in most tissues and that in some pain states, such as neuropathic pain, levels of endocannabinoids are elevated at key sites involved in pain processing. An alternative approach that can be used to harness the potential therapeutic effects of cannabinoids is to maximise the effects of the endocannabinoids, the actions of which are terminated by re-uptake and metabolism by various enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) and cyclooxygenase type 2 (COX2). Preventing the metabolism, or uptake, of endocannabinoids elevates levels of these lipid compounds in tissue and produces behavioural analgesia in models of acute pain. Herein we review recent studies of the effects of inhibition of metabolism of endocannabinoids versus uptake of endocannabinoids on nociceptive processing in models of inflammatory and neuropathic pain.