GABA(B) receptor agonist baclofen has non-specific antinociceptive effect in the model of peripheral neuropathy in the rat.
Baclofen, which is a specific agonist of the metabotropic GABA(B) receptor, is used in clinical practice for the treatment of spasticity of skeletal muscles. It also exerts an analgesic effect, but this effect is still not clear and especially controversial in neuropathic pain. In this work, we studied the antinociceptive effects of baclofen in a model of chronic peripheral neuropathic pain - loose ligation of the sciatic nerve (chronic constriction injury, CCI). As controls we used sham-operated animals. The changes of thermal pain threshold were measured using the plantar test 15-25 days after the operation. The obtained results suggest that baclofen increases pain threshold in both groups. The antinociceptive effect of baclofen was dose-dependent and the maximum response without motor deficits was observed at a dose of 15 mg/kg s.c. In the rats with CCI, significant differences between affected (ipsilateral) and contralateral hind paw were present. This difference was dose-dependent, the highest value (6.2+/-1.37 s) was found at the dose of 20 mg/kg. Based on our results and previous findings it could be summarized that baclofen has antinociceptive action, which is attenuated in the model of chronic neuropathic pain probably due to the degeneration of GABA interneurons after chronic constriction injury.
Franek
M
M
Department of Normal, Charles University, Third Faculty of Medicine, Prague, Czech Republic. franek@lf3.cuni.cz
Vaculín
S
S
Rokyta
R
R
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries; D012585:Sciatica / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
D000700:Analgesics; D018755:GABA Agonists; D001418:Baclofen