George Wilcox, PhD
Professor, Department of Neuroscience
Professor, Department of Neuroscience
Professor, Department of Dermatology
Affiliate Faculty, Institute for Health Informatics (IHI)
Faculty, Graduate Program in Neuroscience
Faculty, MS and PhD Programs in Pharmacology
Neurotransmission of Pain
Dr. Wilcox and colleagues are engaged in research into the spinal neurotransmission of pain and mechanisms underlying hyperalgesia, analgesia and analgesic tolerance. Studies of both excitatory and inhibitory neurotransmission in the rodent spinal cord apply behavioral, electrophysiological (both in vivo and in vitro),immunocytochemical and molecular techniques. Behavioral experiments define biologically relevant interactions, which are then examined at the cellular and molecular level using the more reductionist approaches. A key feature of research projects in this laboratory is open collaboration with laboratories located both here and at other universities.
One major thrust of these investigations examines neurotransmitters thought to mediate major components of excitatory neurotransmission from primary afferent sensory fibers to secondary projection neurons in spinal cord dorsal horn: the excitatory amino acids (EAAs) like glutamate and the neurokinins like substance P. Intense or prolonged excitatory transmission via both these pathways is thought to evoke long term synaptic plasticity and excitotoxicity, which may underlie the development of some chronic pain states.
A second major focus of work in the laboratory is the characterization of several inhibitory neurotransmitters and their receptors which together modulate this excitation. The neurotransmitters, enkephalin, serotonin and noradrenaline, inhibit various components of the incoming excitatory pain message in the dorsal horn via a number of inhibitory receptor subtypes. We are characterizing the interactions between these receptor subtypes and localizing them using transgenic mice, antisense oligonucleotides and immunocytochemical techniques.
Finally, Dr. Wilcox facilitates access for Neuroscience students to high performance computing laboratories on campus - The Laboratory for Computational Science & Engineering and The Minnesota Supercomputer Institute (MSI). High performance computers and visualization are now finding applications in biological imaging, macromolecular modeling and neuronal simulation. A recent neuroscience graduate student developed a new method to optimize correspondence between neuronal simulations and experimental structure-function data.
E Akgün, MM Lunzer, D Tian, M Ansonoff, J Pintar, D Bruce, JE Hawkinson, GL Wilcox and PS Portoghese. FBNTI, a DOR-selective antagonist that allosterically activates MOR within a MOR-DOR heteromer. Biochemistry. 2020 Sep 20. Doi: 10.1021/acs.biochem.0c00498. Online ahead of print. PMID: 32930575
ML Uhelski, D Bruce, R Speltz, GL Wilcox and DA Simone. Topical application of loperamide/oxymorphindole, mu and delta opioid receptor agonists, reduces sensitization of C-fiber nociceptors that possess NaV1.8. Neuroscience. 446: 102-112. doi: 10:1016/j.neuroscience.2020.
Larson, CM, Wilcox, GL & Fairbanks, CA 2019, 'The Study of Pain in Rats and Mice', Comparative Medicine, vol. 69, no. 6, pp. 555-570.
Larson, CM, Wilcox, GL & Fairbanks, CA 2019, 'Defining and Managing Pain in Stroke and Traumatic Brain Injury Research', Comparative Medicine, vol. 69, no. 6, pp. 510-519.
Shah, RM, Peterson, C, Strom, A, Dillenburg, M, Finzel, B, Kitto, KF, Fairbanks, C, Wilcox, G & Wagner, CR 2019, 'Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice', ACS Chemical Neuroscience, vol. 10, no. 10, pp. 4385-4393. https://doi.org/10.1021/acschemneuro.9b00432
Bruce, DJ, Peterson, CD, Kitto, KF, Akgün, E, Lazzaroni, S, Portoghese, PS, Fairbanks, CA & Wilcox, GL 2019, 'Combination of a ?-opioid Receptor Agonist and Loperamide Produces Peripherally-mediated Analgesic Synergy in Mice', Anesthesiology, vol. 131, no. 3, pp. 649-663. https://doi.org/10.1097/ALN.0000000000002840
Krock, E, Millecamps, M, Anderson, KM, Srivastava, A, Reihsen, TE, Hari, P, Sun, YR, Jang, SH, Wilcox, GL, Belani, KG, Beebe, DS, Ouellet, J, Pinto, MR, Kehl, LJ, Haglund, L & Stone, LS 2019, 'Interleukin-8 as a therapeutic target for chronic low back pain: Upregulation in human cerebrospinal fluid and pre-clinical validation with chronic reparixin in the SPARC-null mouse model', EBioMedicine, vol. 43, pp. 487-500. https://doi.org/10.1016/j.ebiom.2019.04.032
Waataja, JJ, Peterson, CD, Verma, H, Goracke-Postle, C, Séguéla, P, Delpire, E, Wilcox, GL & Fairbanks, CA 2019, 'Agmatine preferentially antagonizes GluN2B-containing N-methyl-D-aspartate receptors in spinal cord' Journal of neurophysiology, vol. 121, no. 2, pp. 662-671. https://doi.org/10.1152/jn.00172.2018
Doche, I, Wilcox, GL, Ericson, ME, Valente, NS, Romiti, R, McAdams, BD & Hordinsky, MK 2019, 'Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism' Experimental Dermatology. https://doi.org/10.1111/exd.13835
Barney, CC, Tervo, R, Wilcox, GL & Symons, FJ 2017, 'A case-controlled investigation of tactile reactivity in young children with and without global developmental delay' American Journal on Intellectual and Developmental Disabilities, vol. 122, no. 5, pp. 409-421. https://doi.org/10.1352/1944-7558-122.5.409
Barney, CC, Merbler, AM, Quest, K, Byiers, BJ, Wilcox, GL, Schwantes, S, Roiko, SA, Feyma, T, Beisang, A & Symons, FJ 2017, 'A case-controlled comparison of postoperative analgesic dosing between girls with Rett syndrome and girls with and without developmental disability undergoing spinal fusion surgery' Paediatric anaesthesia, vol. 27, no. 3, pp. 290-299. https://doi.org/10.1111/pan.13066
Uhelski, ML, Bruce, DJ, Séguéla, P, Wilcox, GL & Simone, DA 2017, 'In vivo optogenetic activation of Nav1.8+ cutaneous nociceptors and their responses to natural stimuli' Journal of Neurophysiology, vol. 117, no. 6, pp. 2218-2223. https://doi.org/10.1152/jn.00083.2017
NSCI 4105: Neurobiology Laboratory I (Fall and Summer semesters); NSCI 8221: Neurobiology of Pain and Analgesia (Fall semester)