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, lectrophysiological (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.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Chabot-Doré AJ, Millecamps M, Naso L, Devost D, Trieu P, Piltonen M, Diatchenko L, Fairbanks CA, Wilcox GL, Hébert TE, Stone LS. Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors. Neuropharmacology. 2015 Aug 6;99:285-300.
Wilcox CE, Mayer AR, Teshiba TM, Ling J, Smith BW, Wilcox GL, Mullins PG. The Subjective Experience of Pain: An FMRI Study of Percept-Related Models and Functional Connectivity. Pain Med. 2015 May 19.
Symons FJ, ElGhazi I, Reilly BG, Barney CC, Hanson L, Panoskaltsis-Mortari A, Armitage IM, Wilcox GL. Can Biomarkers Differentiate Pain and No Pain Subgroups of Nonverbal Children with Cerebral Palsy? A Preliminary Investigation Based on Noninvasive Saliva Sampling. Pain Med. 2015 Feb;16(2):249-56.
Chabot-Doré AJ, Schuster DJ, Stone LS, Wilcox GL. Analgesic synergy between opioid and α2 -adrenoceptors. Br J Pharmacol. 2015 Jan;172(2):388-402.
Schuster DJ, Metcalf MD, Kitto KF, Messing RO, Fairbanks CA, Wilcox GL. Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors. Br J Pharmacol. 2015 Jan;172(2):642-53.
Stone LS, German JP, Kitto KF, Fairbanks CA, Wilcox GL. Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects. PLoS One. 2014 Oct 9;9(10):e109903.
Schuster DJ, Kitto KF, Overland AC, Messing RO, Stone LS, Fairbanks CA, Wilcox GL. Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs. J Neurosci. 2013 Aug 14;33(33):13538-46.
Vulchanova L, Schuster DJ, Belur LR, Riedl MS, Podetz-Pedersen KM, Kitto KF, Wilcox GL, McIvor RS, Fairbanks CA. Differential adeno-associated virus mediated gene transfer to sensory neurons following intrathecal delivery by direct lumbar puncture. Mol Pain. 2010 May 28;6:31.
El Ghazi I, Sheng WS, Hu S, Reilly BG, Lokensgard JR, Rock RB, Peterson PK, Wilcox GL, Armitage IM. Changes in the NMR metabolic profile of human microglial cells exposed to lipopolysaccharide or morphine. J Neuroimmune Pharmacol. 2010 Dec;5(4):574-81. Epub 2010 Mar 25.
Overland AC, Kitto KF, Chabot-Doré AJ, Rothwell PE, Fairbanks CA, Stone LS, Wilcox GL. Protein kinase C mediates the synergistic interaction between agonists acting at alpha2-adrenergic and delta-opioid receptors in spinal cord. J Neurosci. 2009 Oct 21;29(42):13264-73.
Fairbanks CA, Stone LS, Wilcox GL. Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis. Pharmacol Ther. 2009 Aug;123(2):224-38. Epub 2009 Apr 23. Review.
Fairbanks CA, Kitto KF, Nguyen HO, Stone LS, Wilcox GL. Clonidine and dexmedetomidine produce antinociceptive synergy in mouse spinal cord. Anesthesiology. 2009 Mar;110(3):638-47.
Riedl MS, Schnell SA, Overland AC, Chabot-Doré AJ, Taylor AM, Ribeiro-da-Silva A, Elde RP, Wilcox GL, Stone LS. Coexpression of alpha 2A-adrenergic and delta-opioid receptors in substance P-containing terminals in rat dorsal horn. J Comp Neurol. 2009 Apr 1;513(4):385-98. Erratum in: J Comp Neurol. 2009 Jun 20;514(6):674.
Schreiber KL, Beitz AJ, Wilcox GL. Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia. Neurosci Lett. 2008 Jul 25;440(1):63-7. Epub 2008 May 17.
Schreiber KL, Beitz AJ, Wilcox GL. Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia. Neurosci Lett. 2008 May 17
Stone LS, Kitto KF, Eisenach JC, Fairbanks CA, Wilcox GL. ST91 [2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride]-mediated spinal antinociception and synergy with opioids persists in the absence of functional alpha-2A- or alpha-2C-adrenergic receptors. J Pharmacol Exp Ther. 2007 Dec;323(3):899-906.
Vit JP, Ohara PT, Tien DA, Fike JR, Eikmeier L, Beitz A, Wilcox GL, Jasmin L. The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception. Pain. 2006 Jan;120(1-2):188-201.
Current Graduate Students:
Rebecca Speltz Paiz (Neuroscience, University of Minnesota).
Former Graduate Students:
Kristin Schreiber (Ph.D. 2004, Neuroscience, University of Minnesota).
Daniel Schuster (Ph.D. 2013, Neuroscience, University of Minnesota).
Aaron Overland (Ph.D. 2010, Neuroscience, University of Minnesota).
Cory Jo Goracke-Postle (Ph.D. 2007, Neuroscience, University of Minnesota).
Lois Jean Kehl (Ph.D. 1996, Neuroscience, University of Minnesota).
Rogene Eichler West (Ph.D. 1996, Neuroscience, University of Minnesota).
Laura Stone (Ph.D. 1999, Neuroscience, University of Minnesota).