The depressive effect of intrathecal clonidine on the spinal flexor reflex is enhanced after sciatic nerve section in rats.
The effect of intrathecal (i.t.) alpha 2-adrenoceptor agonist, clonidine, on the spinal nociceptive flexor reflex was studied in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves or in rats in which the sciatic nerve had been ipsilaterally sectioned. In rats with intact nerves i.t. clonidine caused a dose-dependent biphasic effect on flexor reflex excitability. At low dose (10 ng) the effect of clonidine was purely facilitatory, whereas with 50-100 ng clonidine the initial facilitation was often followed by reflex depression. Long-lasting, strong reflex depression was observed after i.t. injection of high doses of clonidine (1 and 10 micrograms). Four to 18 days after sciatic nerve section, the depressive effect of clonidine on the flexor reflex was dramatically enhanced. Depression was frequently observed already with doses of 5 and 10 ng, and maximal depression was reached at 100 ng and 1 micrograms in axotomized rats. The facilitatory effect of low doses of clonidine on the reflex was also observed, although somewhat less frequently than in normals. The depressive effect of clonidine on the flexor reflex was reversed by the selective alpha 2-receptor antagonist, atipamezole (20 micrograms, i.t.), in rats with both intact and sectioned sciatic nerves. The present results revealed an increased sensitivity and effectiveness of the depression of spinal reflex mechanisms by i.t. clonidine after sciatic nerve section, which is opposite to the decreased sensitivity to i.t. morphine after axotomy that we observed previously.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
Xiao-Jun
XJ
Karolinska Institute, StockholmSweden, Department of Clinical Physiology, Section of Clinical Neurophysiology, Huddinge University Hospital, HuddingeSweden Department of Anaesthesiology, Karolinska Hospital, StockholmSweden.
Puke
Malcolm J C
MJC
Wiesenfeld-Hallin
Zsuzsanna
Z
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003655:Decerebrate State / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D009638:Norepinephrine / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D003000:Clonidine; D009638:Norepinephrine