Carolyn Fairbanks

Carolyn A. Fairbanks, Ph.D.
Associate Professor
Department of Pharmaceutics

Office:
9-143A Weaver-Densford Hall

Telephone Number:
612-625-2945

FAX Number: 
612-626-2125

E-mail Address:
carfair@umn.edu

Education:

B.A., Biology, 1991
Macalester College

Ph.D., Pharmacology, 2000
University of Minnesota

Research Interests:

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.

Dr. Carolyn Fairbanks’s research focuses on development of novel compounds with a pharmacokinetic/dynamic profile ideal for spinal delivery for pain relief. One major focus is the continued characterization and clinical translation of a new compound, moxonidine, as well as its corresponding target, the alpha2C adrenergic receptor. The spinal cord contains alpha2C adrenergic receptors on intrinsic spinal neurons which, when activated by agonists such as moxonidine, inhibit action potentials that transmit the pain signal from the periphery to the brain. Dr. Fairbanks’ studies of moxonidine have used methods that incorporate the use of transgenic mice, antisense oligonucleotides and immunocytochemistry.

A second interest of Dr. Fairbanks’ 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.

Selected Publications:

Goracke-Postle C.J., Overland A.C., Stone L.S. and Fairbanks C.A.  Agmatine transport into spinal nerve terminals is modulated by polyamine analogs.  Journal of Neurochemistry 100(1): 132–141 (2007).

Kitto K.F and Fairbanks C.A.  Supraspinally administered agmatine prevents the development of supraspinal morphine tolerance.  European Journal of Pharmacology 536(1-2): 133-137 (2006).

Goracke-Postle C.J., Nguyen H.O., Stone L.S. and Fairbanks C.A.  Release of tritiated agmatine from spinal synaptosomes.  NeuroReport 17(1): 13-17, 2006.

Roberts J.C., Grocholski B.M., Kitto K.F. and Fairbanks C.A.  Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse.  Journal of Pharmacology and Experimental Therapeutics 314(3): 1226-33 (2005).

King E.W., Audette K.M., Athman G.A., Nguyen H.O.X., Sluka K.A. and Fairbanks C.A.  Transcutaneous nerve stimulation activates peripherally located alpha-2A adrenergic receptors.  PAIN 115(3): 364-373 (2005).

Stone L.S., Wilcox G.L. and Fairbanks C.A.  Moxonidine, a mixed a₂-adrenergic and imidazoline receptor, identifies a novel adrenergic target for spinal analgesia. Annals of the New York Academy of Sciences 1009: 378-385 (2003).  

Zwick M., Molliver D.C., Lindsay J.,  Fairbanks C.A., Sengoku T., Albers K.M. and Davis B.M. Transgenic mice possessing increased numbers of nociceptors do not exhibit increased behavioral sensitivity in models of inflammatory and neuropathic pain.  PAIN 106(3): 491-500 (2003).

Nguyen H.O.X., Goracke-Postle C.J., Kaminski L.L., Overland A.C., Morgan A.D. and Fairbanks C.A.  Neuropharmacokinetic and dynamic studies of agmatine (decarboxylated arginine).  Annals of the New York Academy of Sciences 1009: 82-105 (2003, Dec.)

Kehl L.J. and Fairbanks C.A.  Experimental models of muscle pain. Journal of Exercise and Muscle Physiology, Exercise & Sport Sciences Reviews 31(4): 188-94 (2003).

Fairbanks C.A.  Spinal delivery of analgesics in experimental models of pain and analgesia.  Advanced Drug Delivery Reviews 55(8): 1007-1014 (2003).

Guo X.H., Fairbanks C.A., Stone L.S. and Loh H.H.  DPDPE-UK14,304 synergy is retained in mu opioid receptor knock-out mice.  PAIN 104(1-2): 2098-217 (2003).

Yu C.G., Fairbanks C.A., Wilcox G.L. and Yezierski R.P.  Effects of agmatine, interleukin-10 and cyclosporin on spontaneous pain behavior following excitotoxic spinal cord injury in rats.  Journal of Pain 4: (2003).

Fairbanks C.A., Posthumus I.J., Nguyen H.O., Kitto K.F., Stone L.S. and Wilcox G.L.  Alpha2C adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy.  Journal of Pharmacology and Experimental Therapeutics 300: 282-290 (2002).

Guo A., Simone D.A., Stone L.S., Fairbanks C.A., Wang J. and Elde R. Developmental shift of vannilloid receptor 1 (VR1) terminals into deeper regions of the superficial dorsal horn: correlation with a shift from TRKA to Ret expression by dorsal root ganglion neurons.  European Journal of Neuroscience 14: 293-304 (2001).

Fairbanks C.A., Schreiber K.L., Brewer K.L., Yu C.-G., Stone L.S., Kitto K.F., Nguyen H.O., Grocholski B.M., Shoeman D.W., Kehl L.J., Regunathan S., Reis D.J., Yezierski R.P. and Wilcox G.L.  Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.  Proceedings of the National Academy of Sciences 97(79): 10584-10589 (2000).

Fairbanks C.A. and Wilcox G. L.  Spinal plasticity of acute opioid tolerance . Journal of Biomedical Sciences 7(3): 200-212 (2000).

Fairbanks C.A., Nguyen H.O., Grocholski B.G. and Wilcox G.L.  Moxonidine, an alpha2 adrenergic receptor/imidazoline receptor agonist, synergizes with morphine to inhibit nerve-ligation-induced allodynia in mice.  Anesthesiology 93: 765-773 (2000).

Fairbanks C.A., Posthumus I.J., Kitto K.F., Stone L.S. and Wilcox, G.L. Moxonidine, an alpha2 adrenergic/imidazoline receptor agonist, synergizes with morphine and deltorphin II to inhibit substance P-induced behavior in mice.  PAIN 84(1): 13-20 (2000).

Yu C.G., Marcillo A.E., Fairbanks C.A., Wilcox, G.L. and Yezierski, R.P. Agmatine improves locomotor function and reduces tissue damage following spinal cord injury.  Neuroreport 11: 959-965 (2000).

Fairbanks C.A. and Wilcox, G.L.  Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine.  Journal of Pharmacology and Experimental Therapeutics 288(3): 1107-1116 (1999).

Fairbanks C.A. and Wilcox G.L.  Moxonidine, a selective alpha2-adrenergic and imidazoline receptor agonist, produces spinal antinociception in mice.  Journal of Pharmacology and Experimental Therapeutics 290(1): 403-412 (1999).

Fairbanks C.A. and Wilcox G.L.  Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance. Journal of Pharmacology and Experimental Therapeutics 282: 1408-1417 (1997).

Kehl L.J., Fairbanks C.A., Laughlin T.M. and Wilcox G.L.  Neurogenesis in postnatal rat spinal cord: a study in primary culture.  Science 276: 586-589 (1997).

Stone L.S., Fairbanks C.A., Laughlin T.M., Nguyen H.O., Bushy T.M., Wessendorf M.M. and Wilcox G.L.  Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2.  Neuroreport 8: 3131-3135 (1997).