Antinociceptive effect of systemic gabapentin in mononeuropathic rats, depends on stimulus characteristics and level of test integration.
The anticonvulsant gabapentin is effective against neuropathic pain, but the primary site(s) and mechanism(s) of action are unknown. In order to explore the relative contribution of spinal versus supra-spinal mechanisms to the antinociceptive effect of gabapentin, this study used two differentially integrated nociceptive tests. We systematically compared the effects of various doses of gabapentin on the paw withdrawal to pressure (PWTP), a spinally coordinated reflex and the vocalization threshold to paw pressure (VTPP), a supra-spinal integrated test in the sciatic nerve constriction rat model of neuropathic pain. In addition, we evaluated the effect of gabapentin on the struggle latency to paw immersion into a non-noxious cold (10 degrees C) water bath. Similar lower doses (1-30 mg/kg) of gabapentin produced potent antinociception in the VTPP test but were devoid of effects on the PWTP. The effect was observed not only on the nerve-injured side, but also, although less pronounced, on the contralateral side. Only the highest dose (100 mg/kg) of the anticonvulsant was able to induce an increase in the nerve-injured paw threshold in both tests. In the thermal test, gabapentin (3, 10 and 30 mg/kg i.p.) dose-dependently increased the response time to the 10 degrees C stimulus. Gabapentin at 100 mg/kg but not at 30 mg/kg produced motor deficits in animals using the rotarod test. Taken together, our findings suggest that low doses of gabapentin have a preferential action on the more integrated pain-related behaviour in neuropathic rats. The present results confirm that gabapentin may be a useful approach for the clinical management of several aspects of neuropathic pain.
Kayser
Valérie
V
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U-161, 2 rue d'Alésia, 75014 Paris, France.
Christensen
Dennis
D
D000085:Acetates / Q000627:therapeutic use*; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003080:Cold Temperature; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D006614:Hindlimb / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014828:Vocalization, Animal; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin