Our laboratory studies pain transmission with a special emphasis on
the influence of gender, stress hormones, and immunology. The goal is
to understand painful conditions, such as fibromyalgia syndrome, that
occur more frequently in females, that are exacerbated by stress, and
that are frequently coincident with painful abdominal disorders.
Stress is widely known to influence pain sensitivity. We have found
that urocortins, stress hormones that are related to CRF, enhance
pain sensitivity resulting in chronic mechanical hyperalgesia.
Urocortins recapitulate many characteristics of fibromyalgia and are
elevated in several abdominal disorders that are found in patients
with fibromyalgia. While urocortins attenuate abdominal pain, they
simultaneously induce musculoskeletal hyperalgesia. Tolerance does
not develop to the hyperalgesic effect of urocortins allowing
repeated surges in their synthesis to induce a persistent
hyperalgesia, consistent with the chronic nature of fibromyalgia.
Sex differences in the regulation of urocortin’s synthesis reported
in rodents may explain the higher incidence of fibromyalgia in
females than males.
A second line of study is based on the fact that CRF and urocortins
induce mast cells to degranulate, including those in the CNS. Stress
and certain reproductive hormones, like estrogen, increase mast cell
populations in the thalamus, an area important in sensory
processing. We have found the number of mast cells is further
enhanced by conditions inducing hyperalgesia. Our goal is to
determine the influence of centrally located mast cells on the
regulation of pain and stress responses.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Goudie-DeAngelis EM, Abdelhamid RE, Nunez MG, Kissel CL, Kovács KJ, Portoghese PS, Larson AA. Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice. Pain. 2016 Jul 19;. [Epub ahead of print]
Larson AA, Nunez MG, Kissel CL, Kovács KJ. Intrathecal Urocortin I in the spinal cord as a murine model of stress hormone-induced musculoskeletal and tactile hyperalgesia. Eur J Neurosci. 2015 Aug 31.
Abdelhamid RE, Kovács KJ, Nunez MG, Larson AA. After a cold conditioning swim, UCP2-deficient mice are more able to defend against the cold than wild type mice. Physiol Behav. 2014 Aug;135:168-73.
Larson AA, Pardo JV, Pasley JD. Review of overlap between thermoregulation and pain modulation in fibromyalgia. Clin J Pain. 2014 Jun;30(6):544-55.
Spencer JH, Larson AA, Drake R, Iaizzo PA. A detailed assessment of the human coronary venous system using contrast computed tomography of perfusion-fixed specimens. Heart Rhythm. 2014 Feb;11(2):282-8.
Abdelhamid RE, Kovács KJ, Nunez MG, Larson AA. Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors. Pharmacol Res. 2014 Jan;79:21-7.
Abdelhamid RE, Kovács KJ, Honda CN, Nunez MG, Larson AA. Resiniferatoxin (RTX) causes a uniquely protracted musculoskeletal hyperalgesia in mice by activation of TRPV1 receptors. J Pain. 2013 Dec;14(12):1629-41.
Abdelhamid RE, Kovacs KJ, Pasley JD, Nunez MG, Larson AA. Forced swim-induced musculoskeletal hyperalgesia is mediated by CRF2 receptors but not by TRPV1 receptors. Neuropharmacology. 2013 Sep;72:29-37.
Larson AA, Thomas MJ, McElhose A, Kovács KJ. Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: disruptive effect of cocaine. Brain Res. 2011 Jun 13;1395:30-7. Epub 2011 Apr 28.
Russell IJ and AA Larson: Neurophysiopathogenesis of fibromyalgia syndrome: a unified hypothesis. Rheum Dis Clin N Am 35: 421-435, 2009.
Larson AA and Katalin J. Kovacs. Fibromyalgia, Mechanisms and Treatment, in Treatment of Neuropathis Pain, Schmidt, R.F, & Willis, W.D., Editors, Encyclopedic Reference of Pain. Springer, Berlin Heidelberg New York, 2006, 2010.
Kovacs, Katalin J., Jonathan C. Papic and Alice A. Larson. Movement- evoked hyperalgesia induced by lipopolysaccharides is not suppressed by glucocorticoids. Pain136: 75-84, 2008.
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. Pain136: 75-84, 2008.
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.
“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
Scientific Advisory Board Member for the American Fibromyalgia Association
Former Graduate Students:
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 .