Development of opioid tolerance with repeated transcutaneous electrical nerve stimulation administration
Development of opioid tolerance with repeated transcutaneous electrical nerve stimulation administration
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DOI：
10.1016/s0304-3959(02)00381-0
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发表时间：
2003-03-01
期刊：
影响因子：
7.4
通讯作者：
Sluka, KA
中科院分区：
文献类型：
--
作者：
Chandran, P;Sluka, KA
由低频和高频经皮电神经刺激（TENS）产生的镇痛作用分别由中枢神经系统中μ-或δ-阿片样物质的释放介导。重复给予μ-或δ-阿片激动剂诱导阿片类镇痛耐受。因此，我们测试了在大鼠中重复施用TENS（低或高频率）是否导致对其抗痛觉过敏作用的耐受性的发展，以及对μ-和δ-阿片激动剂的相应交叉耐受性。在成年Sprague-Dawley大鼠中诱导单侧膝关节炎症（3%角叉菜胶）。在氟烷麻醉下，对发炎的膝关节施用低频率（4 Hz）或高频率（100 Hz）TENS，持续6天（每天20分钟）。无TENS对照组仅在同一时间段内给予麻醉。在每天和第六天给予TENS之前和之后测量对机械刺激的退缩阈值。测试单独一组动物对μ-阿片样物质激动剂、吗啡（1.32、3.95、13.2nmol/10 ml，鞘内（i.t.）或δ-阿片激动剂SNC-80（6、20、60、120 nmol/10 ml，i.t.）i.t.局经皮神经电刺激可逆转炎症诱导后机械性缩足阈值的降低。然而，重复给予低或高频率TENS 6天，导致其在第四天逆转同侧继发性机械性痛觉过敏的有效性降低。吗啡在低频率TENS组和SNC-80在高频率TENS组的作用明显小于未接受TENS的组。另一方面，吗啡和SNC-80在高频和低频TENS组中分别与无TENS对照相似。因此，重复给予低频率和高频率TENS导致阿片类药物耐受性的发展，与i.t.分别给予μ-和δ-阿片激动剂。在临床上，可以推断，应避免重复每日TENS给药的治疗方案，以可能阻碍耐受的诱导。(C)2002年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
The analgesia produced by low and high frequency transcutaneous electrical nerve stimulation (TENS) is mediated by the release of mu- or delta-opioids, respectively in the central nervous system. Repeated administration of either mu- or delta-opioid agonists induce opioid analgesic tolerance. Thus, we tested if repeated administration of TENS (either low or high frequency) in rats leads to a development of tolerance to its antihyperalgesic effects with a corresponding cross-tolerance to mu- and delta-opioid agonists. Unilateral knee joint inflammation (3% carrageenan) was induced in adult Sprague-Dawley rats. Either low (4 Hz) or high frequency (100 Hz) TENS was administered for 6 days (20 min daily) to the inflamed knee joint under halothane anesthesia. The no TENS controls were administered anesthesia only for the same period. Withdrawal threshold to mechanical stimuli was measured before and after administration of TENS on each day and also on the sixth day. A separate group of animals was tested for tolerance to either the mu-opioid agonist, morphine (1.32, 3.95, 13.2 nmol/10 ml, intrathecal (i.t.)) or the delta-opioid agonist, SNC-80 (6, 20, 60, 120 nmol/10 ml, i.t.) 30 min after i.t. administration. The reduced mechanical withdrawal threshold following the induction of inflammation was reversed by the application of TENS. However, repeatedly administering either low or high frequency TENS for 6 days, lead to a diminution in its effectiveness in reversing the ipsilateral secondary mechanical hyperalgesia by the fourth day. The effects of morphine in the low and SNC-80 in the high frequency TENS groups were significantly less than the group that did not receive TENS. On the other hand, morphine and SNC-80 were similar to the no TENS control in the high and low frequency TENS groups, respectively. Thus, repeated administration of low and high frequency TENS leads to a development of opioid tolerance with a corresponding cross-tolerance to i.t. administered mu- and delta-opioid agonists, respectively. Clinically, it can be inferred that a treatment schedule of repeated daily TENS administration should be avoided to possibly obviate the induction of tolerance. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.