The effects of morphine, MK-801, an NMDA antagonist, and CP-96,345, an NK1 antagonist, on the hyperesthesia evoked by carageenan injection in the rat paw.
BACKGROUND
The spinal mechanisms underlying the hyperesthetic state during inflammation are little understood. To gain a better understanding of these mechanisms, this study evaluated the effects of intrathecal morphine; MK-801, an N-methyl-D aspartic (NMDA) antagonist; and CP-96,345, an NK1 antagonist, on the hyperesthesia observed after carageenan injection of the rat paw.


METHODS
In rats injected with 2 mg carageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carageenan injection. Drugs were administered 2 h after the carageenan injection. The magnitude of hyperesthesia was evaluated with the difference score (DS), which was calculated by subtracting the PWL of the untreated paw from the PWL of the injected paw.


RESULTS
Intrathecal morphine increased PWLs of both the injected and the untreated paws equally in a dose-dependent manner, but intrathecal morphine did not affect the level of DS. Intrathecal MK-801 increased PWLs of the injected paw to the level of the untreated paw in a dose-dependent manner and increased the DS levels. Intrathecal CP-96,345 had no effect on PWLs of either the injected or the untreated paw. Coadministration of MK-801 with morphine reduced the DS for each dose of morphine.


CONCLUSIONS
These data indicate that (1) an NMDA receptor, but not an NK1 receptor, plays an important role in maintaining the hyperesthesia after carageenan injection; and (2) NMDA antagonism has a simple additive interaction with morphine in the carageenan model of inflammatory hyperesthesia.
Yamamoto
T
T
Department of Anesthesiology, Chiba University School of Medicine, Japan.
Shimoyama
N
N
Mizuguchi
T
T
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D002351:Carrageenan; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006941:Hyperesthesia / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D015287:Neurokinin B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001713:Biphenyl Compounds; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D009020:Morphine; D015287:Neurokinin B; D002351:Carrageenan; C066892:CP 96345