Role of nitric oxide in the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat.
BACKGROUND
Nitric oxide (NO) has been shown to be involved in mediating nociceptive information transmission in the spinal cord. It is known that the N-methyl-D-aspartate receptor plays an important role in the development of the spinal facilitation evoked by a protracted small afferent input and that this effect is mediated at least in part by NO. Recently, it has been found that N-methyl-D-aspartate receptor-mediated spinal facilitation is crucial in the development of thermal hyperesthesia evoked by a nerve constriction injury. In the current study, we investigated the role of NO in the development of thermal hyperesthesia after a nerve constriction injury.


METHODS
The Bennett and Xie model (four loose chromic gut ligations around the rat sciatic nerve) was used to examine the development of thermal hyperesthesia. An NO synthase inhibitor (N omega-nitro-L-arginine or N omega-nitro-L-arginine methyl ester hydrochloride), rat hemoglobin, or L-arginine was administered intrathecally 10 min before the nerve injury (pretreatment study) or 15 min after the nerve injury (posttreatment study).


RESULTS
Pretreatment but not posttreatment administration of NO synthase inhibitor significantly delayed the development of thermal hyperesthesia. The effect of NO synthase inhibitor was reversed by the coadministration of L-arginine but not by the coadministration of D-arginine. Pretreatment with rat hemoglobin also delayed the development of thermal hyperesthesia. L-Arginine itself had no effect on the development of thermal hyperesthesia.


CONCLUSIONS
NO may play an important role in the development of N-methyl-D-aspartate receptor-mediated spinal facilitation after a nerve constriction injury.
Yamamoto
T
T
Department of Anesthesiology, School of Medicine, Chiba University, Japan.
Shimoyama
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003250:Constriction; D006358:Hot Temperature; D006941:Hyperesthesia / Q000209:etiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries*
D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester