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.)
- Waataja JJ, Peterson CD, Verma H, Goracke-Postle CJ, Séguéla P, Delpire E, Wilcox GL, Fairbanks CA. Agmatine preferentially antagonizes GluN2B-containing N-methyl-D-aspartate receptors in spinal cord. J Neurophysiol. 2018 Nov 14. doi: 10.1152/jn.00172.2018.
- Doolen S, Cook J, Riedl M, Kitto K, Kohsaka S, Honda CN, Fairbanks CA, Taylor BK, Vulchanova L. Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling. Glia. 2017;65:1976-1989.
- Peterson CD, Kitto KF, Akgün E, Lunzer MM, Riedl MS, Vulchanova L, Wilcox GL, Portoghese PS, Fairbanks CA. Bivalent ligand that activates mu opioid receptor and antagonizes mGluR5 receptor reduces neuropathic pain in mice. Pain. 2017;158:2431-2441.
- Laoharawee K, Podetz-Pedersen KM, Nguyen TT, Evenstar LB, Kitto KF, Nan Z, Fairbanks CA, Low WC, Kozarsky KF, McIvor RS. Prevention of neurocognitive deficiency in mucopolysaccharidosis type II mice by central nervous system-directed, AAV9-mediated iduronate sulfatase gene transfer. Hum Gene Ther. 2017;28(8):626-638
- 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;759:169-181.
- 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.Br J Pharmacol. 2015;172:642-653.
- 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;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;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;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;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;33:13538-46.
- Winter TN, Elmquist WF, Fairbanks CA. OCT2 and MATE1 provide bidirectional agmatine transport. Mol Pharm. 2011;8:133-42.
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).