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Targeting the Endocannabinoid System for Management of Chemotherapy, HIV and Antiretroviral-Induced Neuropathic Pain
Abstract:
Chemotherapeutic drugs (used for treating cancer), HIV infection and antiretroviral therapy (ART) can independently cause difficult-to-manage painful neuropathy. Paclitaxel, a chemotherapeutic drug, for example is associated with high incidence of peripheral neuropathy, around 71% of the patients of which 27% of these develop neuropathic pain. Use of cannabis or phytocannabinoids has been reported to improve pain measures in patients with neuropathic pain, including painful HIV-associated sensory neuropathy and cancer pain. Phytocannabinoids and endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), produce their effects via cannabinoid (CB) receptors, which are present both in the periphery and central nervous system. Endocannabinoids are synthesized in an “on demand” fashion and are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). Various studies, including those from our group, suggest that there are changes in gene and protein expression of endocannabinoid molecules during chemotherapy-induced neuropathic pain (CINP), HIV and antiretroviral-induced neuropathic pain. Analysis of endocannabinoid molecule expression in the brain, spinal cord and paw skin using LC-MS/MS show that there is a specific deficiency of the endocannabinoids 2-AG and/or anandamide in the periphery during CINP. Various drugs including endocannabinoids, cannabidiol, inhibitors of FAAH and MGL, CB receptor agonists, desipramine and coadministered indomethacin plus minocycline have been found to either prevent the development and/or attenuate established CINP, HIV and antiretroviral-induced neuropathic pain in a CB receptor-dependent manner. The results available suggest that targeting the endocannabinoid system for prevention and treatment of CINP, HIV-associated neuropathic pain and antiretroviral-induced neuropathic pain is a plausible therapeutic option.

Sep 24, 2020 04:00 PM in London

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Speakers

Willias Masocha
Dr @Faculty of Pharmacy, Kuwait University
Willias Masocha is an Associate Professor in the Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait. He received his Bachelor of Pharmacy Honours from the University of Zimbabwe in 1997 and Ph.D. degree in Pharmacology from the University of Granada, Spain, in 2002. He was a Postdoctoral Fellow & International Brain Research Organization Research Fellow in Prof. Krister Kristensson’s lab at the Department of Neuroscience, Karolinska Institutet, Sweden, from 2003 to 2006 working on the role of the immune system on the entrance of parasites into the CNS and the neuropathogenesis of African trypanosomiasis. His research program at Kuwait University focuses on studying the pathophysiology of various types of pain, especially chemotherapy and antiretroviral drug-induced neuropathic pain, and evaluation of the activities of potential anti-inflammatory and/or analgesic drugs including the cannabinoids.