Ph.D., Medical College of Georgia, 1991
Pain Neurobiology, Tachykinin/Neruokinin systems, Estrogens and pain
Our research program examines the role that gene expression of various neurotransmitters and their receptors plays in the regulation of sensory function, and particularly focuses of the role of neurokinin (NK-1) receptors in chronic inflammatory pain. The affinity and coupling of spinal NK-1 receptors is altered during persistent pain. Studying the expression, coupling and trafficking of these receptors will clarify how their plasticity contributes to the central sensitization and increased responsiveness to subsequent stimuli (hyperalgesia and allodynia) that are hallmarks of chronic pain.
Areas of the brain involved in the regulation of affect (or mood) are affected by pain. Our studies have implicated hippocampal neurogenesis as an important mood-regulating process that can be regulated by environmental factors including persistent nociception. This research has shown that chronic pain activates cellular and molecular mechanisms of depression, and suggests that their common co-morbidity may have a fundamental neurological foundation.
Our research also investigates gender-related differences in pain sensation. Our results show that estrogen modifies the expression of NK-1 and BDNF genes in pain pathways as well as in higher brain centers associated with emotions and mood. Currently we are exploring sites and mechanisms of estrogens' actions in the nervous system that may underly how men and women sense pain differently, and how estrogens may exacerbate some pain syndromes.
We also study the role of neurokinin-expressing sensory nerves in cutaneous wound healing; topical opioids impair wound healing, and we have evidence that they may do so by suppressing the release of sensory neuropeptides. Understanding the relationship between sensory nerves, neuropeptides, opioids and their receptors in modulating wound healing will have direct implications concerning evolving pharmacological approaches to treating wound pain in humans.
This research has important consequences related to our understanding of pain and inflammation by clarifying the involvement of neurokinin receptor function in the sensitization of the central nervous system by long-term pain, and may identify novel targets or therapies for the control of the sensitizing effects of chronic pain resulting from neurokinin receptor plasticity.
Allen, A.L. and McCarson, K.E. Estrogen increases nociception-evoked brain-derived neurotrophic factor gene expression in the female rat. Neuroendocrinology 81 (2005)193-199. PMID: 16020928
Winter, M.K. and McCarson, K.E. G-protein activation by neurokinin-1 receptors is dynamically regulated during persistent nociception. Journal of Pharmacology and Experimental Therapeutics 315 (2005) 214-221. PMID: 15985614
Enna, S.J., and McCarson, K.E. The role of GABA in the mediation and perception of pain. Advances in Pharmacology 54 (2006) 1-27. PMID: 17175808
Duric, V. and McCarson, K.E. Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. Journal of Pain 7 (2006) 544-555. PMID: 16885011
Rook, J.M., Hasan, W., and McCarson, K.E. Temporal effects of topical morphine application on cutaneous wound healing. Anesthesiology 109(2008)130-136. PMID: 18580183; PMCID: PMC2598738
Liverman C., Brown, J., Sandhir, R., Klein, R., McCarson, K.E., and Berman, N.J. Role of the estrogen receptors GPR30 and ERα in peripheral sensitization: relevance to trigeminal pain disorders in women. Cephalalgia 29 (2009) 729-741. PMID: 19220308
Davis, P.F., Ozias, M.K., Carlson, S.E., Reed, G.A., Winter, M.K., McCarson, K.E., and Levant, B. Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): Interactions with reproductive status. Nutritional Neuroscience 13 (2010) 161-169. PMID: 20670471; PMCID: PMC2955509
Ghose, S, Winter, M. K., McCarson, K.E., Tamminga, C.A., and Enna, S.J. The GABAB receptor as a target for antidepressant drug action. British Journal of Pharmacology 162 (2011) 1-17. Epub 2010 Dec 6. PMID: 20735410; PMCID: PMC3012402
Stucky, N.L, Gregory, E., Winter, M.K., He, Y.Y., Hamilton, E., McCarson, K.E., and Berman, N.E. Sex differences in behavior and expression of CGRP-related genes in a rodent model of chronic migraine. Headache 51 (2011) 674-692. PMID:21521205
Gupta, S., McCarson, K.E., Welch, K.M.A., and Berman, N.E.J. Mechanisms of pain modulation by sex hormones in migraine. Headache 51 (2011) 905-922. PMID: 21631476