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Vol. 303, Issue 3, 1199-1205, December 2002
2
-1
Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with
Antiallodynic Effects of Gabapentin
Departments of Anesthesiology (Z.D.L., E.S.H., C.R.V., Y.-H.S.,
C.I.S., R.R.M.), Pathology (N.A.C., R.R.M.), and Chemistry/Biochemistry
(C.R.V.), University of California San Diego, La Jolla, California
The calcium channel 
2
-1 subunit is a structural
subunit important for functional calcium channel assembly. In vitro
studies have shown that this subunit is the binding site for
gabapentin, an anticonvulsant that exerts antihyperalgesic effects by
unknown mechanisms. Increased expression of this subunit in the spinal cord and dorsal root ganglia (DRG) has been suggested to play a role in
enhanced nociceptive responses of spinal nerve-injured rats to
innocuous mechanical stimulation (allodynia). To investigate whether a
common mechanism underlies allodynic states derived from different
etiologies, and if so, whether similar 2-1 subunit up-regulation correlates with these allodynic states, we compared DRG
and spinal cord 2-1 subunit levels and gabapentin
sensitivity in allodynic rats with mechanical nerve injuries (sciatic
nerve chronic constriction injury, spinal nerve transection, or
ligation), a metabolic disorder (diabetes), or chemical neuropathy
(vincristine neurotoxicity). Our data indicated that even though
allodynia occurred in all types of nerve injury investigated, DRG
and/or spinal cord 2-1 subunit up-regulation and
gabapentin sensitivity only coexisted in the mechanical and diabetic
neuropathies. Thus, induction of the 2-1 subunit in
the DRG and spinal cord is likely regulated by factors that are
specific for individual neuropathies and may contribute to
gabapentin-sensitive allodynia. However, the calcium channel
2-1 subunit is not the sole molecular change that
uniformly characterizes the neuropathic pain states.
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