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Dr. Mokha has been engaged in pain and analgesia research for over 30 years and has spent the last 10 years in advancing our understanding of the biological mechanisms, a) that make women more susceptible to the development of pain syndromes such as migraine, irritable bowel syndrome and fibromyalgia, and b) that generate sex-related differences in the response to analgesics. These investigations at systems, cellular and molecular levels have provided evidence that estrogen attenuates the analgesic function of many G- protein- coupled receptors (GPCRs) present in the spinal cord. These GPCRs include opioid receptors and a2-adrenoceptors, and many are known to mediate descending inhibition of pain in the spinal cord. Estrogen attenuates or abolishes the analgesic response elicited by activation of opioid receptor like 1 (ORL1) receptor and a2-adrenoceptors in the female whereas testosterone is required for the expression of the analgesic response in the male. Although we showed previously that estrogen attenuates the expression of the ORL1 receptor gene, more recent studies in the laboratory are also unraveling the contribution of membrane estrogen receptors in attenuating the analgesic response through non-genomic mechanisms. These studies will provide important new perspective into the treatment of pain, particularly in women at different phases of their life (pre-puberty, reproductive years, pregnancy and menopause) and in aging men. Considering the widespread distribution of these GPCRs in the brain and their involvement in multiple functions, these findings will have a broader relevance. Presently, I serve as the Chair of the Internal Advisory Committee for the RCMI grant.
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