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Alice A. Larson, Ph.D. Professor, Departments of Veterinary Pathobiology, Neuroscience and Pharmacology E-mail: larso011@umn.edu

Research Interests:

Our laboratory studies pain transmission with a special emphasis on the influence of gender and immunology. The goal is to understand painful conditions, such as fibromyalgia syndrome, which occur more frequently in females and are exacerbated by stress. Our focus is on mast cells, immune cells that enter the CNS in response to stress and certain reproductive hormones.

Mast cells are localized in the thalamus, an area important in sensory transmission, including pain. Mast cells are more abundant in specific areas of the female than the male thalamus. We found that interfering with the degranulation of mast cells by central injection of cromolyn, a mast cell stabilizer, blocks the acquisition of appropriate breeding behaviors in female mice, perhaps by an influence on sensory transmission.

Stress also increases mast cells in the thalamus. The classic increase in HPA activity by restraint stress in mice is enhanced and prolonged by central injection of cromolyn prior to restraint. This suggests that one role of mast cells is to protect against excessive stress responses.

Our studies will determine (1) the biochemical signals that recruit mast cells to the brain, (2) the anatomical distribution of mast cells in response to pain and stress, and (3) the influence of thalamic mast cells on the regulation of pain and stress responses.

Selected Publications:

(For a comprehensive list of  Dr. Larson's recent publications , refer to PubMed, a service provided by the National Library of Medicine.)

Larson, Alice A. and Katalin J. Kovács: Fibromyalgia, Mechanisms and Treatment, in Treatment of Neuropathic Pain, Schmidt, R.F, & Willis, W.D., Editors, Encyclopedic Reference of Pain. Springer, Berlin Heidelberg New York, 2006, on-line 2007.

Kovács KJ, Papic JC, Larson AA. Movement-evoked hyperalgesia induced by lipopolysaccharides is not suppressed by glucocorticoids. Pain. 2007 Aug 6.

Taiwo OB, Russell IJ, Mignot E, Lin L, Michalek JE, Haynes W, Xiao Y, Zeitzer JM, Larson AA. Normal cerebrospinal fluid levels of hypocretin-1 (orexin A) in patients with fibromyalgia syndrome. Sleep Med. 2007 Apr;8(3):260-5. Epub 2007 Mar 21.

Kovacs KJ, Larson AA. Mast cells accumulate in the anogenital region of somatosensory thalamic nuclei during estrus in female mice. Brain Res. 2006 Oct 9;1114(1):85-97.

Taiwo OB, Kovacs KJ, Larson AA. Chronic daily intrathecal injections of a large volume of fluid increase mast cells in the thalamus of mice. Brain Res. 2005 Sep 14;1056(1):76-84.

Taiwo OB, Kovacs KJ, Sun Y, Larson AA. Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice. Pain. 2005 Mar;114(1-2):131-40.

Taiwo, Oludare B., Katalin J. Kovács, Lauren C. Sperry and Alice A. Larson: Naloxone-induced morphine withdrawal increases the number and degranulation of mast cells in the thalamus of the mouse. Neuropharmacology 46: 824-835, 2004.

Kehl, Lois J., Katalin J. Kovács, Alice A. Larson: Tolerance develops to the effect of lipopolysaccharides on movement-evoked hyperalgesia when administered chronically by a systemic but not an intrathecal route. Pain 111: 104-115 2004.

Current Funding

“Thalamic Mast Cells Inhibit HPA Activity”, Academic Health Center at the University of Minnesota

Honors and Awards

National Institute of Mental Health (NIMH) Study Section Member, Behavioral Neurobiology Subcommittee, 1988–1992

National Institute on Drug Abuse (NIDA) Career Development Award, 1988–1993

SmithKline Beecham Award for Research Excellence, 1995

Associate Editor for the Journal of Pharmacology and Experimental Therapeutics , 1999–2000

Recent Graduate Student

Nelson L. Dalo, D.V.M. (M.S. 1984, Veterinary Physiology and Pharmacology), currently an Associate Professor of Pharmacology

James Madl, D.V.M. (Ph.D. 1987, Veterinary Physiology and Pharmacology), currently Assoc Professor at Colorado State University

Stephen Skilling, D.V.M. (Ph.D. 1989, Veterinary Biology) currently a practicing veterinarian in Burnsville , MN

Carl Hornfelt (M.S. 1990; Ph.D. 1998, Veterinary Biology) currently a researcher at Medtronics

Sun Xiaofeng, M.S. 1990; Ph.D. 1993, Veterinary Biology) currently a researcher at Mayo Clinic

Julie Kreeger, D.V.M., M.S., Ph.D. 1995, Veterinary Biology) currently a researcher at the National Black-Footed Ferret Conservation Center, Laramie WY

Virginia Geottl (D.V.M./Ph.D. 1996, Neuroscience, University of Minnesota).  Currently a Research Associate at The Ohio State University .

Susan L. Giovengo D.V.M. (Ph.D. 1997, Veterinary Biomedical Sciences, University of Minnesota) Currently at The Proctor and Gamble Co., Mason OH

Ruben Velazquez (M.D./Ph.D. 1998, Neuroscience, University of Minnesota).  Currently a physician specializing in ear, nose and throat in Puerto Rico .