Pain-related response and nociceptive processing in the central nervous system. Modification by diltiazem, morphine or clonidine

The present study was undertaken to examine the pain-related response induced by peripheral injection of mustard oil(MO) and its nociceptive processing in the central nervous system in rats. Pain-related response was evaluated by measuring the frequencies of flinching after injection of MO in the paw. Flinching was significantly higher with 5 and 20% MO than with 1%, flinching being most prominent with 20% MO and steadily observed from 15 min to 60 min after injection. Local spinal cord glucose utilization (LSGU) and local cerebral glucose utilization (LCGU) were measured using the <14>^C-2-deoxyglucose method. The binding sites of substance P(SP) receptor (XK-1) and L-type Ca channel were examined by in vitro autoradiography using ^<125>I-Bolton Hunter (BH)-SP and 3^H-PN200-110 as ligands. With injection of 20%MO, LSGU was increased(16, 19%) in laminae I-II of the ipsilateral spinal cord (C5, C7). Similar metabolic increase(14%) was seen also in laminae V-VI of C5 spinal cord. There was no significant change in LCGU. The binding sites of ^<125>I-BH-SP was decreased (18～26%) in laminae I-II in the ipsilateral spinal cord. 3H-PN200-110 binding was increased(9～15%) in laminae I-II in the spinal cord when compared to the contralateral side. L-type Ca channel antagonist, diltiazemQOmg・kg^<-1> or 20mg・kg^<-1>, iv) suppressed flinching in a dose related manner. Narcotic analgesic, morphine (2.5 mg・kg^<-1>, iv) and α_2 agonist clonidine (150μg・kg^<-1>, ip) suppressed flinching. Morphine and clonidine suppressed also the increase in LCGU, the decrease in SP receptor binding and the increase in L-type ca channel binding. The results indicate that the pain induced with MO is transmitted to dorsal horn of the spinal cord, particularly to laminae I-II. where SP is released and L-type Ca channel is opened. It is also indicated that pain modulating action of morphine and clonidine is related in part to the suppression of SP release in dorsal horn. The results also suggest that the transmission of noxious stimulation is partly regulated by an aincrease in intracellular Ca.

侵害刺激

脊髄・脳

ブドウ糖代謝

サブスタンスP受容体

L型Caチャネル