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Wellcome Trust conference The Challenges of Chronic Pain

11-13 March 2015
Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

Abstract deadline: 30 January 2015
Registration deadline: 16 February 2015

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Archive workshop and seminar slides Professor Peter Karmerman…
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Past Research
Cannabinoid signalling in the pain pathway
While the psychotropic and medicinal use of cannabis has been appreciated for millennia, it is only recently that endocannabinoids and their cognate receptors and synthesising and degrading enzymes have been identified. Because of its many similarities with the opioid system this has spurred interests to harness the cannabinoid system as a target for potential novel analgesic drugs. In addition to their role in pain modulation, endocannabinoids have now been recognized as powerful signalling molecules involved in such diverse functions as memory and amelioration of exitotoxicity. Two G-protein-coupled receptors have been identified as the main target for endogenous and exogenous cannabinoids. The CB1 Receptor is found throughout the brain, spinal cord and peripheral neurons, whereas the CB2 receptor is found on non-neuronal cells including glia cells. While it is generally thought that the classic tetrad of cannabinoids (hypolocomotion, antinociception, hypothermia, and catalepsy) and its psychotopic properties are a reflection of CB1 activation in the CNS, the presence of CB1 receptors on primary sensory neurons has rekindled an interest in the peripheral action of cannabinoids in antinociception. This is attractive from a drug development point of view, because of the possibility to divorce supraspinal side effects from antinociceptive action by designing drugs incapable of crossing the blood brain barrier or by regional intrathecal delivery.
The projects therefore uses a range of techniques to study the expression pattern of CB1 receptors and their function in dorsal root ganglia and spinal cord in normal animals, during development and in animal models of inflammatory or neuropathic pain. Receptor expression is studied using immunohistochemistry and rtPCR while the function of CB1 receptor activation is assessed in cultured sensory neurons using calcium imaging or in situ using a skin nerve in vitro preparation. The aim of this study is to define the action of CB1 receptors in peripheral sensory neurons and to critical appraise their potential as analgesic drug targets.