Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat.
OBJECTIVE
Spinal gamma-aminobutyric acid (GABA) receptors have been shown to modulate post-nerve injury-induced allodynia. This study sought to examine the antiallodynic effects of a GABA analog gabapentin [1-(aminomethyl)cyclohexaneacetic acid], given by subarachnoid injection in a rat neuropathic pain model.


METHODS
The rats were prepared with lumbar subarachnoid catheters, and allodynia was induced in rats by ligation of the L5-6 nerve roots (Chung model).


RESULTS
Spinal injection of gabapentin resulted in a dose-dependent (10-1,000 microg) antagonism of the allodynia at doses that had no detectable effect on motor function. Subarachnoid injection of either the GABA A antagonist bicuculline (0.3 microg), or the GABA B antagonist CGP 35348 (30 microg) 5 minutes before or 60 minutes after injection of GABA receptor agonist did not reverse the antiallodynic effects produced by gabapentin.


CONCLUSIONS
Gabapentin shows antiallodynic effect, but its mechanism is not known. The failure to reverse this effect by GABA A or B antagonists at doses that reverse the effects of the respective agonists suggests that gabapentin is involved in the modulation of spinal systems by mechanisms that do not involve either a GABA A or a GABA B site.
Hwang
J H
JH
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
Yaksh
T L
TL
D000085:Acetates / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000588:Amines; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002404:Catheterization; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D000077206:Gabapentin; D008026:Ligation; D008297:Male; D018908:Muscle Weakness / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013346:Subarachnoid Space / Q000502:physiology*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D018712:Analgesics, Non-Narcotic; D003509:Cyclohexanecarboxylic Acids; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin