The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat.
This study evaluated the effects of spinal gamma-aminobutyric acid (GABA) receptor agonists on the tactile allodynia observed in rats with ligation of the L5/L6 nerve roots (Chung model) and chronic lumbar intrathecal catheters. In these rats, the spinal injection of the GABAB agonist baclofen (BAC; 0.03-03 micrograms) and GABAA agonist muscimol (MUS; 0.1-1.0 micrograms) resulted in a dose-dependent antagonism of the allodynia at doses which had no detectable effect upon motor function. Intrathecal injection of the GABAB antagonist CGP 35348 (CGP; 30 micrograms) or the GABAA antagonist bicuculline (BIC; 0.3 micrograms) prior to injection of each GABA receptor agonist had little effect upon normal or tactile allodynic thresholds, but significantly reversed the anti-allodynic effects produced by the respective receptor agonists. The antagonistic effects were limited to the agonist of the respective receptor. These observations indicate that spinal GABAA and GABAB receptors modulate spinal systems activated by low threshold mechanoreceptors which mediate the allodynia observed following peripheral nerve injury.
Hwang
J H
JH
Department of Anesthesiology, University of California San Diego, La Jolla 92093-0818, USA.
Yaksh
T L
TL
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002404:Catheterization; D018755:GABA Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010149:Postoperative Pain / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology* / Q000601:surgery*; D013126:Spinal Nerve Roots; D014110:Touch / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D009118:Muscimol; C066430:CGP 35348; D001640:Bicuculline