Lérida M, Sánchez-Blázquez P, Garzón J
Department of Neuropharmacology, Cajal Institute, C.S.I.C., Madrid, Spain.
Neurosci Lett. 1987 Oct 16;81(1-2):155-8. doi: 10.1016/0304-3940(87)90357-0.
The development of tolerance to and dependence on morphine was studied in a model of experimental chronic pain in the rat (Freund's adjuvant-induced arthritis). Animals were rendered tolerant by subcutaneous implantation of 3 pellets of 75 mg morphine base each. Those pain-suffering rats developed tolerance to the analgesic effect of the alkaloid at a slower rate than control animals. Moreover, upon treatment with naloxone, these morphine-tolerant-dependent rats from the model, showed a lower incidence of several withdrawal symptoms, particularly jumping, chattering, ptosis, writhing, body shakes and squeaking on touch. These findings suggest that animals suffering from chronic pain present an altered physiological response to the continuous inhibitory effect of exogenous opioids. These differences do not seem to involve cAMP mediated mechanisms since 3-isobutyl-1-methylxanthine (IBMX) administration did not distinguish between control and arthritic rats.
在大鼠实验性慢性疼痛模型（弗氏佐剂诱导的关节炎）中研究了对吗啡的耐受性和依赖性的发展。通过皮下植入3粒每粒含75mg吗啡碱的药丸使动物产生耐受性。那些遭受疼痛的大鼠对生物碱镇痛作用产生耐受性的速度比对照动物慢。此外，在用纳洛酮治疗时，来自该模型的这些吗啡耐受依赖性大鼠出现几种戒断症状的发生率较低，特别是跳跃、颤搐、眼睑下垂、扭体、身体颤抖和触摸时尖叫。这些发现表明，患有慢性疼痛的动物对外源性阿片类药物的持续抑制作用呈现出改变的生理反应。这些差异似乎不涉及cAMP介导的机制，因为给予3-异丁基-1-甲基黄嘌呤（IBMX）并未区分对照大鼠和关节炎大鼠。
