The spinal cord carries pain signals to the brain via excitatory neurotransmission and contains most of the same inhibitory neurotransmission systems as the brain. Spinal delivery of analgesics that activate such inhibitory systems offers a very selective method of pain control that can increase the therapeutic index of such analgesics by reducing or eliminating their exposure to brain regions that mediate undesired side effects.
A primary interest of Dr. Fairbanks's team includes understanding the basic spinal neural mechanisms (glutamate-induced plasticity) governing induction chronic pain as well as opioid-induced tolerance and addiction. Her laboratory currently researches the role of an endogenous amine, agmatine (decarboxylated arginine), in those biological events. Studies of glutamatergic and agmatinergic neurotransmission in the spinal cord apply behavioral, biochemical, immunocytochemical and molecular techniques. Acquiring such information may lead to the development of a novel class of spinally delivered drugs intended for reversing (rather than alleviating) the effects of chronic pain.
(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.
Fairbanks CA, Goracke-Postle CJ. Neurobiological studies of chronic pain and analgesia: Rationale and refinements. Eur J Pharmacol. 2015 Jul 15;759:169-81.
Guedon JM, Wu S, Zheng X, Churchill CC, Glorioso JC, Liu CH, Liu S, Vulchanova L, Bekker A, Tao YX, Kinchington PR, Goins WF, Fairbanks CA, Hao S. Current gene therapy using viral vectors for chronic pain. Mol Pain. 2015 May 13;11:27.
Schuster DJ; Metcalf MD; Kitto KF; Messing RO; Fairbanks CA; Wilcox GL. Ligand requirements for involvement of PKCepsilon in synergistic analgesic interactions between spinal mu and delta opioid receptors. British Journal of Pharmacology. 172(2):642-53, 2015 Jan
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, Belur LR, Riedl MS, Schnell SA, Podetz-Pedersen KM, Kitto KF, McIvor RS, Vulchanova L, Fairbanks CA. Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5. Front Neuroanat. 2014 Aug 5;8:66. doi: 10.3389/fnana.2014.00066. eCollection 2014.
Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR, McIvor RS, Elde RP, Fairbanks CA, Vulchanova L. Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front Neuroanat. 2014 Jun 10;8:42. doi: 10.3389/fnana.2014.00042. eCollection 2014.
Fairbanks CA, Peterson CD, Speltz RH, Riedl MS, Kitto KF, Dykstra JA, Braun PD, Sadahiro M, Salton SR, Vulchanova L. The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity. Pain. 2014 Jul;155(7):1229-37.
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.
Winter TN, Elmquist WF, Fairbanks CA. OCT2 and MATE1 provide bidirectional agmatine transport. Mol Pharm. 2011 Feb 7;8(1):133-42.
Pan G, Winter TN, Roberts JC, Fairbanks CA, Elmquist WF. Organic cation uptake is enhanced in bcrp1-transfected MDCKII cells. Mol Pharm. 2010 Feb 1;7(1):138-45.
Riedl MS, Braun PD, Kitto KF, Roiko SA, Anderson LB, Honda CN, Fairbanks CA, Vulchanova L. Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing. J Neurosci. 2009 Oct 21;29(42):13377-88.
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.
Wade CL, Eskridge LL, Nguyen HO, Kitto KF, Stone LS, Wilcox G, Fairbanks CA. Immunoneutralization of agmatine sensitizes mice to micro-opioid receptor tolerance. J Pharmacol Exp Ther. 2009 Nov;331(2):539-46.
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.
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.
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.
Goracke-Postle CJ, Overland AC, Riedl MS, Stone LS, Fairbanks CA. Potassium- and capsaicin-induced release of agmatine from spinal nerve terminals. J Neurochem. 2007 Sep;102(6):1738-48.
Goracke-Postle CJ, Overland AC, Stone LS, Fairbanks CA. Agmatine transport into spinal nerve terminals is modulated by polyamine analogs. J Neurochem. 2007 Jan;100(1):132-41.
Former Graduate Students:
Cory Jo Goracke-Postle (Ph.D. 2007, Neuroscience, University of Minnesota).
Aaron Overland (Ph.D. 2010, Neuroscience, University of Minnesota).
Daniel Schuster (Ph.D. 2013, Neuroscience, University of Minnesota).