Zou Wang-yuan, Guo Qu-lian, Cai Jin, Wang E, Yang Hong-wei, Xu Dao-miao, Wang Yi-chun
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 May;33(5):404-9.
To evaluate the effect of intrathecal pumping tramadol on cell-mediated immunity in rats with formalin inflammatory pain.
Thirty-two Sprague-Dawley adult male rats weighting 250 approximately 300 g were randomly divided into 4 groups (n=8 in each group):Saline group (NS) and 3 tramadol groups (T1,T2,and T3). The rats were anesthetized with intraperitoneal chloral hydrate (300 approximately 350)mg/kg. Microspinal catheter was inserted into the subarachnoid space at the lumber region according to modified Yaksh techniques. In the tramadol groups,after 5 days tramadol was continuously infused through the spinal catheter at 50 (T1),25 (T2), and 12.5 microg/h (T3) for 7 days. In the NS group normal saline was continuously infused instead of tramadol. On Day 7 formalin (5%, 50 microL) was injected into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking was recorded for 60 min.Pain intensity scoring(PIS)(0 approximately 3;0= no pain, 3=severe pain) was used to assess the antinociceptive effect of intrathecal tramadol. The rats were killed after the evaluation of pain intensity. Body weight and spleen weight were measured and spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin-A(ConA) induced splenocyte proliferation. A modified lactic acid dehydrogenase(LDH) release assay was done to assess the NK cell activity. Phenotypic expressions of cell surface markers of T lymphocyte subsets (CD3+, CD3+ CD4+, CD3+ CD8+, and CD4+/ CD8+) and NK cell(CD161+) in the spleen were analyzed by flow cytometry.
The PIS scores were significantly lower in the T1,T2,and T3 groups than those in the NS group. The spleen index and splenocyte proliferation induced by ConA were significantly suppressed in the T1 group,and the phenotypes of T lymphocyte subsets were significantly changed,but no significant difference was found in the T2 and T3 groups compared with the NS group. There were no differences in NK cell activity in the 3 tramadol groups from the control group.
Intrathecal pumping tramadol has significantly antinociceptive effect. Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity. General analgesic dosage tramadol (25 and 12.5 microg/h) has no effect on the immune function.
评估鞘内注射曲马多对福尔马林炎性疼痛大鼠细胞介导免疫的影响。
将32只体重约250～300 g的成年雄性Sprague-Dawley大鼠随机分为4组（每组n = 8）：生理盐水组（NS）和3个曲马多组（T1、T2和T3）。大鼠腹腔注射水合氯醛（300～350）mg/kg麻醉。根据改良的Yaksh技术，将微脊髓导管插入腰段蛛网膜下腔。在曲马多组中，5天后通过脊髓导管以50（T1）、25（T2）和12.5 μg/h（T3）的速度持续输注曲马多7天。在NS组中，持续输注生理盐水而非曲马多。在第7天，将5%福尔马林（50 μL）注射到左后足底表面。记录60分钟内的退缩次数、舔舐次数和总舔舐时间。采用疼痛强度评分（PIS）（0～3；0 = 无疼痛，3 = 严重疼痛）评估鞘内曲马多的镇痛效果。在评估疼痛强度后处死大鼠。测量体重和脾脏重量，并计算脾脏指数（脾脏重量/体重）。基于刀豆蛋白A（ConA）诱导的脾细胞增殖评估T淋巴细胞功能。采用改良的乳酸脱氢酶（LDH）释放试验评估NK细胞活性。通过流式细胞术分析脾脏中T淋巴细胞亚群（CD3+、CD3+ CD4+、CD3+ CD8+和CD4+/CD8+）和NK细胞（CD161+）细胞表面标志物的表型表达。
T1、T2和T3组的PIS评分显著低于NS组。T1组的脾脏指数和ConA诱导的脾细胞增殖受到显著抑制，T淋巴细胞亚群的表型发生显著变化，但与NS组相比，T2和T3组无显著差异。3个曲马多组的NK细胞活性与对照组无差异。
鞘内注射曲马多具有显著的镇痛作用。鞘内注射高剂量曲马多（50 μg/h）可抑制T淋巴细胞增殖并改变T淋巴细胞亚群表型，但不影响NK细胞活性。一般镇痛剂量的曲马多（25和12.5 μg/h）对免疫功能无影响。
