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.)
- Kissel CL, Kovács KJ, Larson AA. Evidence for the modulation of nociception in mice by central mast cells. Eur J Pain. 2017;21:1743-1755.
- Pardo JV, Lee JT, Larson RC, Thuras P, Larson AA. Automated quantitation of cold-inducible human brown adipose tissue with FDG PET/CT with application to fibromyalgia. Am J Nucl Med Mol Imaging. 2017;7:24-32.
- 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;157:2561-2570
- 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;42:2772-82.
- 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;135:168-73.
- Larson AA, Pardo JV, Pasley JD. Review of overlap between thermoregulation and pain modulation in fibromyalgia. Clin J Pain. 2014;30:544-555.
- 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;11:282-288.
- 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;79:21-27.
- 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;14:1629-41.
- 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;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;1395:30-7
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 .