Tsai Yu-Chuan, Won Shen-Jeu, Lin Mao-Tsun
Pain Management Section, Department of Anesthesiology, National Cheng Kung University, College of Medicine, 138 Sheng-Li Road, Tainan 704, Taiwan Department of Microbiology and Immunology, National Cheng Kung University, College of Medicine, Tainan, Taiwan Department of Physiology, School of Medicine and Life Science, National Yang-Ming University, Taipei, Taiwan.
Pain. 2000 Nov;88(2):155-160. doi: 10.1016/S0304-3959(00)00323-7.
We investigated the effects of acute and of chronic morphine treatment on T-lymphocyte function and natural killer (NK) cell activity in rats receiving chronic constriction injury (CCI) of the sciatic nerve. T-Lymphocyte function was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced splenocyte proliferation. The effects of morphine on thermal hyperalgesia were also assessed by measuring paw withdrawal latency (PWL) in rats. All of the rats that received CCI developed thermal hyperalgesia while sham-operated rats did not. Thermal hyperalgesia was dose-dependently reversed after acute (single injection) and after chronic (daily injection for 7 days) administration of morphine but persisted in saline-treated CCI rats. There was no significant difference between sham and saline-treated CCI groups in splenocyte proliferation and NK cell activity. NK cell activity and splenocyte proliferation induced by ConA and PHA were significantly suppressed by acute morphine treatment in a dose-dependent manner. The reversal of the thermal hyperalgesia persisted throughout the period of chronic morphine treatment. No tolerance to the suppression of NK cell activity and splenocyte proliferation was observed after chronic morphine treatment. These data suggest that both acute and chronic morphine treatment can cause a dose-dependent reversal of thermal hyperalgesia and inhibition of NK cell activity and splenocyte proliferation in rats with sciatic CCI, without concomitant development of tolerance. Opioid therapy for chronic neuropathic pain should be used cautiously, especially in immune-compromised cases.
我们研究了急性和慢性吗啡治疗对坐骨神经慢性压迫损伤（CCI）大鼠T淋巴细胞功能和自然杀伤（NK）细胞活性的影响。基于伴刀豆球蛋白A（ConA）和植物血凝素（PHA）诱导的脾细胞增殖来评估T淋巴细胞功能。还通过测量大鼠的爪退缩潜伏期（PWL）来评估吗啡对热痛觉过敏的影响。所有接受CCI的大鼠均出现热痛觉过敏，而假手术大鼠则未出现。急性（单次注射）和慢性（每日注射7天）给予吗啡后，热痛觉过敏呈剂量依赖性逆转，但在生理盐水处理的CCI大鼠中持续存在。假手术组和生理盐水处理的CCI组在脾细胞增殖和NK细胞活性方面无显著差异。急性吗啡治疗以剂量依赖性方式显著抑制了ConA和PHA诱导的NK细胞活性和脾细胞增殖。热痛觉过敏的逆转在慢性吗啡治疗期间持续存在。慢性吗啡治疗后未观察到对NK细胞活性和脾细胞增殖抑制的耐受性。这些数据表明，急性和慢性吗啡治疗均可导致坐骨神经CCI大鼠的热痛觉过敏呈剂量依赖性逆转，并抑制NK细胞活性和脾细胞增殖，但不会同时产生耐受性。对于慢性神经性疼痛的阿片类药物治疗应谨慎使用，尤其是在免疫功能低下的病例中。
