Time-dependent effect of morphine and time-independent effect of MK-801, an NMDA antagonist, on the thermal hyperesthesia induced by unilateral constriction injury to the sciatic nerve in the rat.
BACKGROUND
It is known that peripheral nerve injury induces time-dependent changes in dorsal horn function. The current study investigated the time dependency of the effects of intrathecal morphine and MK-801, an N-methyl-D-aspartate antagonist, on the thermal hyperesthesia evoked by unilateral constriction injury to the sciatic nerve in the rat.


METHODS
In rats with a unilateral constriction injury to the sciatic nerve, paw withdrawal latency against thermal stimulation for the injured paw was typically 3 s less than that for the uninjured paw during the first 5 weeks after the injury. Drugs were administered intrathecally 1 or 5 weeks after the nerve injury.


RESULTS
Intrathecal morphine increased the paw withdrawal latencies of both the injured paw and the uninjured paw in an equally dose dependent manner in the 1-week study. In the 5-week study, morphine increased the paw withdrawal latency of the uninjured paw in a dose-dependent manner, but not that of the injured paw. Intrathecal MK-801 increased the paw withdrawal latency of the injured paw to the level of the uninjured paw in a dose-dependent manner in both the 1- and 5-week studies.


CONCLUSIONS
These data indicate that (1) an N-methyl-D-aspartate receptor-mediated spinal facilitation may be the common mechanism maintaining the thermal hyperesthesia evoked by the constriction injury, and (2) the effects of intrathecal morphine on this thermal hyperesthesia are time-dependent.
Yamamoto
T
T
Department of Anesthesiology, School of Medicine, Chiba University, Japan.
Shimoyama
N
N
Asano
H
H
Mizuguchi
T
T
D000818:Animals; D003251:Constriction, Pathologic; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006941:Hyperesthesia / Q000209:etiology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012584:Sciatic Nerve / Q000293:injuries*; D013997:Time Factors
D009270:Naloxone; D016291:Dizocilpine Maleate; D009020:Morphine