Okuyama S, Aihara H
J Pharmacobiodyn. 1985 Jan;8(1):56-63. doi: 10.1248/bpb1978.8.56.
Single neuronal activity was recorded extracellularly in the ventrobasal (VB) nucleus of the thalamus in non-adjuvant arthritic rats under urethane (1200 mg/kg, i.p.) anesthesia. The effects of morphine and indomethacin on the evoked responses elicited by noxious stimuli such as transcutaneous electrical stimulation (TES) or tibial nerve electrical stimulation (TNES), or non-noxious stimulation such as repetitive brushing were examined. Intravenous administered morphine (0.1, 0.3 and 1 mg/kg) depressed the evoked responses elicited by either TES or TNES without affecting any background activities. In contrast, intravenous administered indomethacin (1, 3 and 10 mg/kg) depressed the evoked responses induced by TES, but failed to depress the evoked responses induced by TNES. At doses of 3 and 10 mg/kg, indomethacin slightly depressed the background activities of the nociceptive neurones. Depressant effects of morphine were restored by intravenous naloxone (0.5 mg/kg) administration, but not observed in case of indomethacin. The evoked responses induced by non-noxious stimulation failed to depress either indomethacin or morphine administration. These results suggest that the site of action of indomethacin in non-adjuvant arthritic rats is mainly in the periphery. In contrast, morphine produced an antinociceptic action due to the central mechanism.
在氨基甲酸乙酯(1200mg/kg,腹腔注射)麻醉下,对非佐剂性关节炎大鼠丘脑腹侧基底(VB)核进行细胞外单神经元活动记录。研究了吗啡和吲哚美辛对经皮电刺激(TES)或胫神经电刺激(TNES)等伤害性刺激或重复刷擦等非伤害性刺激所诱发反应的影响。静脉注射吗啡(0.1、0.3和1mg/kg)可抑制TES或TNES诱发的反应,且不影响任何背景活动。相比之下,静脉注射吲哚美辛(1、3和10mg/kg)可抑制TES诱发的反应,但不能抑制TNES诱发的反应。在3和10mg/kg剂量时,吲哚美辛可轻微抑制伤害性神经元的背景活动。静脉注射纳洛酮(0.5mg/kg)可恢复吗啡的抑制作用,但吲哚美辛则未观察到这种情况。非伤害性刺激诱发的反应在注射吲哚美辛或吗啡后均未受到抑制。这些结果表明,吲哚美辛在非佐剂性关节炎大鼠中的作用部位主要在外周。相比之下,吗啡通过中枢机制产生抗伤害作用。