Kenneth E McCarson, PhD
Ph.D., Medical College of Georgia, 1991
Pain Mechanisms, G-Protein Coupled Receptor Function, Spinal Cord Injury Outcomes
My research program examines the role that gene expression of various neurotransmitters and their receptors plays in the regulation of sensory function, and has focused on the role of neurokinin (NK-1) receptors in chronic inflammatory pain. The number, 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. Through several productive collaborative studies, I study changes in function of several different G-protein coupled receptors (NPY, MOR) in the setting of persistent pain or other long-term activation states.
Areas of the brain involved in the regulation of affect (or mood) are affected by pain. My 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.
Projects in my laboratory also investigate 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. We are exploring sites and mechanisms of estrogens' actions in the nervous system that may underlie how men and women sense pain differently, and how estrogens may exacerbate some pain syndromes. Recently, our research has focused on developing rodent behavioral models of migraine headache, which is much more prevalent in women than men. Our migraine model has allowed us to investigate the effects of environmental estrogens that can worsen migraine frequency or severity.
As the Director of the KUMC Rodent Behavior Facility, I also contribute to several exciting projects that require detailed behavioral assessment of rats or mice. In the largest of these projects, I provide detailed analysis of gait and motor function in a rat model of spinal cord injury to assess the impact of therapeutic interventions based on neural progenitor cells or brain-machine interface devices. Another funded collaborative project focuses on the development of mutant mouse models of undiagnosed genetic diseases that lead to intellectual or developmental disorders in humans.
McCarson, K.E., and Krause, J.E. NK-1 and NK-3 type tachykinin receptor mRNA expression in the rat spinal cord dorsal horn is increased during adjuvant or formalin-induced nociception. Journal of Neuroscience, 14 (1994) 712-720. PMID: 830135919.
Mogil, J.S., and McCarson, K.E. Identifying pain genes: bottom-up and top-down approaches. Journal of Pain 1 [Suppl. 1] (2000) 66-80. PMID: 14622845
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
McCarson, K. E. How to Become a 'Rat Whisperer' - 7 Tips on Handling Lab Rodents. Laboratory Animal Welfare Compliance 1(2010) 13-15.
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
Corder, G., Doolen, S., Donahue, R.R., Winter, M.K., Jutras, B.L., He, Y., Hu, X., Wieskopf, J.S., Mogil, J.S., Storm, D.R., Wang, Z.J., McCarson, K.E., and Taylor, B.K. Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science. 341  (2013) 1394-1399. PMID: 24052307; PMC Journal in Process. (Cover Article)
Krizsan-Agbas D, Winter MK, Eggimann LS, Meriwether J, Berman NE, Smith PG, McCarson KE. Gait analysis at multiple speeds reveals differential functional and structural outcomes in response to graded spinal cord injury. J Neurotrauma. 2014 May 1;31(9):846-56. doi: 10.1089/neu. 2013.3115. Epub 2014 Apr 7. PMID: 24405378
McCarson KE, Enna SJ. GABA Pharmacology: The Search for Analgesics. Neurochem Res. 2014 Oct;39(10):1948-63. doi: 10.1007/s11064-014-1254-x. Epub 2014 Feb 15. PMID: 24532294
Vermeer LM, Gregory E, Winter MK, McCarson KE, Berman NE. Behavioral effects and mechanisms of migraine pathogenesis following estradiol exposure in a multibehavioral model of migraine in rat. Exp Neurol. 2014 Sep 25. pii: S0014-4886(14)00294-5. doi: 10.1016/j.expneurol. 2014.09.011. [Epub ahead of print] PMID: 25263582