The effect of intrathecal guanfacine and clonidine on the flexor reflex in rats with intact and sectioned sciatic nerves.
We examined the effect of intrathecal (i.t.) administration of the non-selective alpha 2-adrenoceptor agonist clonidine and the alpha 2A-adrenoceptor selective agonist guanfacine on flexor reflex excitability in decerebrate, spinalized, unanesthetized rats before and after unilateral section of the sciatic nerve. Both guanfacine and clonidine dose dependently depressed the flexor reflex in rats with intact nerves. There was a dramatic increase in the sensitivity of the flexor reflex to the depressive effect of i.t. clonidine 4 to 18 days after sciatic nerve section. In contrast, the sensitivity to i.t. guanfacine increased only slightly. The present results suggest that the markedly increased sensitivity to the analgesic effect of the non-selective alpha 2-adrenoceptor agonist does not involve up-regulation of alpha 2A-adrenoceptors. Since radioligand binding data suggested that about 4% of spinal cord alpha 2-adrenoceptors are of the alpha 2C type, whereas alpha 2B-adrenoceptors are not detectable, alpha 2C-adrenoceptors seem to be a good candidate to mediate the up-regulated response to clonidine in axotomized rats. Thus, alpha 2C-adrenoceptor agonists may be useful in the treatment of neuropathic pain.
Xu
X J
XJ
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
Wikberg
J E
JE
Wiesenfeld-Hallin
Z
Z
D000698:Analgesia; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012584:Sciatic Nerve / Q000502:physiology*; D015854:Up-Regulation
D016316:Guanfacine; D003000:Clonidine