Involvement of Spinal Synaptic Modulation of Calcium Channel and Intracellular Enzyme Activities in Nitrous Oxide-induced Analgesia and Its Tolerance

笑気鎮痛とその耐震発現における脊髄シナプス調節機序：N型Caチャネルおよびprotein kinase Cの関与

Involvement of Spinal Synaptic Modulation of Calcium Channel and Intracellular Enzyme Activities in Nitrous Oxide-induced Analgesia and Its Tolerance

Creators Tsuruta Junko

He present study was undertaken to examine whether N2O-induced analgesia and its tolerance are mediated by the change in calcium channel and PKC activities that are closely related to calcium influx and neurotransmitter release. Three series of the study were performed in male Wistar rats. 1) Time course of analgesic effect of N_2O (75%) was examined in the rats exposed for the first 2-hr followed by the second 2-hr after 1-hr intermission. Analgesic effect was assessed by %MPE (tail-flick latency). 2) The binding sites of 125I-<y-conotoxin (CgTx) : N-type calcium channel, 3^H-PN 200-110 : L-type calcium channel, ^<125>I-MK-801 : NMDA receptor, and 3^H-PDBu : PKC activity were determined by using in vitro autoradiography. 3) The effects of nimodipine, ω-CgTx, MK-801, or staurosporine (PKC inhibitor) on tolerance to N_2O- induced analgesia were examined. N_2O produced potent analgesia, the %MPE being increased to a maximum of 79% at 30 min. During the second exposure, %MPE was not increased throughout 120 min, suggesting that acute tolerance occurred. ^<125>I-ω-CgTx binding significantly decreased by 20% in the Rexed I-II of the spinal cord during the first exposure, while ^3H-PN-200-110 or ^<125>I-MK-801 binding did not change. During the second exposure restoration of ^<125>I-ω-CgTx binding and increase in 3^H-PDBu binding (13%) were observed. Calcium entry blocker or NMDA receptor antagonist reversed tolerance to N_2O analgesia, the magnitude being in the order of ω-CgTx>MK801>nimodipine. Specific antagonist of PKC (staurosporine), strongly reversed the tolerance and produced analgesia. The present study demonstrated that suppression of calcium influx possibly through α_2 receptor activation coupled with N-type calcium channel play an important role in N_2O-induced analgesia. The results also demonstrated that tolerance to N_2O-induced analgesia was produced by the PKC activation /translocation evoked by increased Ca^<2+>i.

[ISSN]0513-1731

[NCID]AN00243156