Effects of intrathecal nonnarcotic analgesics on chronic tactile allodynia in rats: alpha 2-agonists versus somatostatin analog.
The effects of the intrathecal alpha 2-agonists tizanidine and clonidine and the somatostatin analog octreotide on an experimental rat model of tactile allodynia were investigated to determine the therapeutic potential for treating chronic neuropathic pain. Allodynia was induced by ligating the rat sciatic nerve. The mechanical threshold for paw withdrawal was assessed by applying von Frey hairs to quantify analgesic actions. Mean 50% paw withdrawal thresholds were converted to the percentage of maximum possible effect (%MPE) where %MPE = (postdrug threshold-predrug threshold) divided by (15 g-predrug threshold) x 100. Dose-response curves were plotted for suppression of paw withdrawal 30 minutes after intrathecal injection of various doses of tizanidine, clonidine, and octreotide. Thresholds on the non-lesioned side were greater than 15 g. The lesioned side had baseline thresholds of less than 4.5 g. Dose-response curves were established for the antiallodynia effects of each drug. Tizanidine and clonidine at a 25-micrograms dose increased the threshold to greater than 97% of the MPE, but caused transient hindpaw weakness or sedation. No side effect was observed at a 10-micrograms dose, at which the threshold was 88-96% of MPE. Intrathecal octreotide modestly increased the threshold to only 49-67% of MPE, showing a lesser analgesic effect, although no side effect was observed at a 4-micrograms dose. The antiallodynic effects of intrathecal tizanidine and clonidine were more potent than that of octreotide.
Ono
N
N
Department of Neurosurgery, Gunma University School of Medicine, Maebashi, Japan.
Kroin
J S
JS
Penn
R D
RD
Paice
J A
JA
D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives*
D013004:Somatostatin; C023754:tizanidine; D003000:Clonidine; D015282:Octreotide