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Carolyn Fairbanks, Ph.D.
Assistant Professor, Departments of Pharmaceutics and Neuroscience
carfair@mail.ahc.umn.edu
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 Spinal
Delivery of Analgesics.
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’ team includes understanding the
basic spinal neural mechanisms (glutamate-induced plasticity) governing
induction of 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.
Fig. 2 (above). Reduction in moxonidine-mediated antinociception and
 2CAR-ir
after chronic treatment with 2CAR-antisense
ODN. A) moxonidine dose-response curves in mice treated with
vehicle [ED50 = 0.29 nmol (0.019-0.045); circles], mismatch ODN [ED50
= 0.034 nmol (0.025-0.047); squares], and 2CAR-antisense
ODN [ED50 = 0.17 nmol (0.11-0.26); triangles]. Error bars represent
mean ± S.E.M. for each dose point (n = 6-8 mice/dose). When SP was
given to mice in the absence of moxonidine, the number of behaviors
did not differ between saline-treated (48 ± 2.4, n = 8), mismatch-treated
(41 ± 4.9, n = 6), and 2CAR-antisense-treated
(42 ± 4.7, n = 6) mice (ANOVA, p > 0.05). B) 2CAR-ir
was present in the superficial dorsal horn of mice treated with vehicle.
C) 2CAR-ir
was absent in dorsal horn of the mice treated with 2C
AR-antisense ODN. D) 2CAR-ir
was present in the dorsal horn of mice treated with mismatch ODN.
E) 2AAR-ir
was present in the dorsal horn of mice treated with 2CAR-antisense
ODN. F) 2AAR-ir
was present in the dorsal horn of mice treated with mismatch ODN.
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Selected Publications
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Fairbanks, C.A.
Spinal delivery of analgesics in experimental models of pain and analgesia.
Adv
Drug Deliv Rev. 2003 Aug 28;55(8):1007-41 |
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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 2002; 300:282-290
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Guo, A., Simone, D.A., Stone, L.S., Fairbanks, C.A.,
Wang, J., 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 2001;14:293-304 |
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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., Wilcox,
G.L. Agmatine reverses pain induced by inflammation, neuropathy, and
spinal cord injury.
Proceedings
of the National Academy of Sciences 2000; 97(79):10584-10589 |
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Fairbanks, C.A., Nguyen, H. O., Grocholski, B.G., Wilcox,
G. L.
Moxonidine, an alpha2 adrenergic receptor/imidazoline receptor agonist,
synergizes with morphine to inhibit nerve-ligation-induced allodynia
in mice.
Anesthesiology
2000; 93:765-773 |
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Fairbanks, C.A., Posthumus, I.J., Kitto, K.F., Stone,
L.S., 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
2000; 84(1):13-20 |
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