Lois J. Kehl, D.D.S. Ph.D.
Assistant Professor
Office: 612-626-0411
Lab: 612-624-6625
lois@mail.ahc.umn.edu (preferred)
kehlx001@umn.edu
Research Interests
The overriding goal of my research program is to translate preclinical and clinical pain research to new clinical therapeutics for musculoskeletal pain and other clinically relevant pain complaints. The wealth of preclinical and clinical pain researchers at the University of Minnesota provides an ideal setting to accomplish this goal. The Minnesota Center for Pain Research provides a framework for interactions among this group of multidisciplinary investigators and a resource for clinicians who manage pain.
Current Research Projects
A feasibility study to evaluate whether pathological biochemical and anatomical changes in the cerebrospinal fluid and intervertebral discs of patients scheduled for surgical treatment of chronic low back pain due to degenerative disc disease correlate with disability and subjective pain report. Physical evaluation and pain assessments obtained just prior to and six months after surgery will allow us to relate these changes to clinically observable parameters. Given the context of a feasibility study, the current study will examine a limited number of pre-selected neurological and inflammatory mediators (e.g. cytokines, opioid peptides and receptors) for which strong rationale exist. This project is a collaborative effort among students, residents, and faculty in the Departments of Anesthesiology, Neuroscience, Physical Medicine and Rehabilitation, the Twin Cities Spine Center and the U of M Research Services Organization.
A large clinical study to determine whether levels of selected biochemical mediators are altered in human skeletal muscle or synovial fluid during painful episodes in subjects with certain pain diagnoses of the jaw or temporomandibular joint (TMJ). I currently lead this basic science project which is part of an NIH-sponsored multi-site clinical research project (NIH UO1 DEO13331, P.I.: Eric Schiffman) to validate research diagnostic criteria for certain musculoskeletal pain diagnoses of the jaw. In collaboration with investigators at the University of Minnesota Cancer Center, the basic science team on this project is developing biochemical methods to measure selected pronociceptive compounds using high performance liquid chromatography (HPLC) and mass spectrometry in skeletal muscle and synovial fluid. If this project finds that different levels of certain biochemicals exist in painful muscle relative to nonpainful muscle then these compounds may be useful as biologic markers to distinguish muscle pain diagnoses (e.g. fibromyalgia vs. myofascial pain syndrome), as targets for novel pharmacologic agents to more effectively manage chronic muscle pain and as important clues to mechanisms underlying these pain states.
An NIH-sponsored TMJ Implant Registry and Repository (NIH N01 DE22635, P.I. James Fricton; www.tmjregistry.org) whose primary purpose is to provide surgically harvested TMJ implants and associated tissues to researchers investigating mechanisms of human pain and dysfunction related to placement of these materials. My role in this project is to conduct pilot studies investigating possible correlations between the neural and biochemical responses to different TMJ implant materials and reported TMJ hyperalgesia. The local response of peripheral nerves in the TMJ to alloplastic implants will be characterized by performing immunohistochemistry studies on the explant tissues to detect changes in innervation. These studies will evaluate density of unmyelinated primary afferent (sensory) innervation, the density of sympathetic innervation, and the density of axonal sprouting that occurred in the presence of implant material. Biochemical studies will employ methods developed in #2 above to measure changes in pronociceptive biochemicals in soft tissues associated with TMJ implants.
Preclinical studies using a rodent model of musculoskeletal pain that I developed and validated during my postdoctoral research training. This model is unique in that it employs a direct dependent measure of musculoskeletal pain: the peak force exerted by rodent forelimbs. This model has been used in published studies investigating mechanisms of inflammatory muscle pain, bone cancer pain, and fibromyalgia.
Selected Publications
Kehl, L.J., Kovacs, K.J. and Larson, A.A. (in press) Tolerance develops to the effect of lipopolysaccharides on movement-evoked hyperalgesia when administered chronically by a systemic but not an intrathecal route. Pain.
Radhakrishnan, R., Bement, M.K.H., Skyba, D.A., Kehl, L.J. and Sluka, K.A. (2004) Models of Muscle Pain: Carrageenan Model and Acidic Saline Model. Current Protocols in Pharmacology. 5.35.1-5.35.27.
Kehl, L.J. and Fairbanks, C.A. (2003) Experimental Models of Muscle Pain. Exercise and Sport Sciences Reviews. 31(4):188-194.
Kehl, L.J., Hamamoto, D.T., Wacnik, P.W., Wilcox, G.L., Croft, D.L., Norsted, B.D., Wilcox, G.L. and Simone, D.A. (2003) The Cannabinoid Receptor Agonist WIN 55,212-2 Attenuates Muscle Hyperalgesia Associated with Inflammation and Osteolytic Tumor Growth. Pain. 103:175-186.
Wacnik, P.W., Kehl, L.J., Trempe, T.M., Ramnaraine, M.L., Beitz, A.J. and Wilcox, G.L. (2003) Osteolytic Tumor Implantation in Mouse Humerus Evokes Movement-related Hyperalgesia Exceeding that Evoked by Intramuscular Carrageenan. Pain. 101(1-2):175-186.
Fairbanks, C.A., Schreiber, K.M., Brewer, K.L., Stone, L.S., Kitto, K.F., Nguyen, H.O., Grocholski, B.M., Shoeman, D., Kehl, L.J., Regunathan, S., Reis, D.J., Yezierski, R.P., Wilcox, G.L. (2000) Spinal agmatine reverses pain induced by inflammation, neuropathy and spinal cord injury. Proc. Natl. Acad. Sci. USA 97(19):10584-10589
Kehl, L.J., Trempe, T.M. and Hargreaves, K.M. (2000) A new animal model for assessing mechanisms and management of muscle hyperalgesia. Pain 85:333-343.
Kehl, L.J., Fairbanks, C., Laughlin, T. and Wilcox, G.L. (1997) Neurogenesis in postnatal rat spinal cord: a study in primary culture. Science 276:586-589.