Physiology

KARIN WESTLUND HIGH, Ph.D. Professor Ph.D. University of Texas Medical Branch, 1981 Office: MS-609 Medical Center 0298 Lab: MS-635, MS-639A-F, Tel: 323-3668, 323-0673 E-mail: karin.high@uky.edu Curriculum Vita (pdf)

Our studies are designed to understand (1) how sensitization of pain pathways can lead to persistent pain states and (2) how inflammatory pain can be alleviated. In response to tissue injury and pain, an amplified neurogenic drive is generated in the spinal cord dorsal horn. Nerve impulses then propagate back out to the peripheral injury site bringing neurotransmitter signals that directly impact inflammatory responses. Three neuroinflammatory models are being utilized to examine neurotransmitter activation and to promote reduction of inflammation and pain: (1) temporomandibular joint pain, (2) inflammatory pain in the knee joint, and (3) a model of visceral pain resembling chronic human pancreatitis. Treatment strategies, such as gene therapy and transdermal delivery of opioid peptides for site specific anti-nociceptive action, are being utilized to stop the activation caused by neurotransmitters for both the pancreatitis and muscle/joint inflammatory models. Information about the interface between the nervous system and the immune system is being generated, including the potential for tissue repair promoted by opioid peptides. Our investigations have led to discovery of a new visceral pain pathway and a new acid sensing G-coupled receptor in the knee joint lining. We are also developing new strategies for the treatment of chronic pain, inflammation and tissue repair after injury.

Recent publications:

McNearney TA, Ma Y, Chen Y, Taglialatela G, Yin H, Zhang WR, Westlund KN. A peripheral neuroimmune link: glutamate agonists upregulate NMDA NR1 receptor mRNA and protein, vimentin, TNF-alpha, and RANTES in cultured human synoviocytes. Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R584-98. PMID: 20007519 http://www.ncbi.nlm.nih.gov/pubmed/20007519

Kochukov MY, McNearney TA, Yin H, Zhang L, Ma F, Ponomareva L, Abshire S, Westlund KN. Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain. 2009 Aug 20;5:49. PMID: 19695100 http://www.ncbi.nlm.nih.gov/pubmed/19695100

Ma F, Zhang L, Westlund KN. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons. Mol Pain. 2009 Jun 17;5:31. PMID: 19531269 http://www.ncbi.nlm.nih.gov/pubmed/19531269

Westlund, KN, Vera- Portocarrero, LP, Zhang, L,Wei, J, Quast, MJ, Palmer, SN, Cleeland, CS. fMRI of supraspinal areas after morphine and one week pancreatic inflammation. NeuroImage, 44: 23-34, 2009.
http://dx.doi.org/10.1016/j.neuroimage.2008.07.048

Other Publications