The effects of intrathecal morphine and clonidine on the prevention and reversal of spinal cord hyperexcitability following sciatic nerve section in the rat.
We have previously shown that intrathecal (i.t.) morphine, but not the alpha 2-adrenoreceptor agonist clonidine, administered prior to sciatic nerve section, reduced the level of autotomy in rats, which is a behavioural model of neuropathic pain. Neither drug was effective when administered 15 min after nerve section. We now examined the effects of i.t. morphine and clonidine on the development of flexor reflex hyperexcitability following sciatic nerve section in acute physiological experiments. The flexor reflex was recorded from the hamstring muscles in decerebrate, spinalized, unanesthetized rats. The effect of sciatic nerve section on the flexor reflex without drugs was compared with axotomy performed 60 min after i.t. injection of 3 micrograms or 30 micrograms morphine, as well as 50 micrograms clonidine. The effect of these drugs on reversing reflex hyperexcitability was also examined. Both doses of morphine administered prior to sciatic nerve section profoundly depressed the baseline reflex and the higher dose almost completely abolished reflex hyperexcitability following nerve section. In contrast, clonidine pre-administration was less effective in depressing the baseline reflex and blocked reflex hyperexcitability less than morphine. Both morphine and clonidine administered 15 min after nerve section reversed spinal hyperexcitability. Thus, the ability of morphine to prevent the occurrence of autotomy may be related to its effectiveness in blocking axotomy-induced hyperexcitability. These physiological data suggest that even a short period of spinal cord hyperexcitability following nerve injury may lead to the development of neuropathic pain.
Luo
L
L
Karolinska Institute, Section of Clinical Neurophysiology, Huddinge Hospital, HuddingeSweden Karolinska Institute, Department of Anaesthesiology and Intensive Care, Karolinska Hospital, StockholmSweden.
Puke
C M J
CMJ
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004576:Electromyography / Q000187:drug effects; D005260:Female; D007278:Injections, Spinal; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology
D009020:Morphine; D003000:Clonidine