Analgesic effect of thalidomide on inflammatory pain
Analgesic effect of thalidomide on inflammatory pain
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DOI：
10.1016/s0014-2999(99)00918-8
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发表时间：
2000-03-10
影响因子：
5
通讯作者：
Cunha, FQ
中科院分区：
文献类型：
--
作者：
Ribeiro, RA;Vale, ML;Cunha, FQ
肿瘤坏死因子α（TNF-α）可能在大鼠机械炎症痛觉过敏的发生和小鼠伤害性扭体反应中发挥关键作用。沙利度胺已被证明可以选择性抑制 TNF-α 的产生。因此，我们研究了沙利度胺对这些反应以及小鼠热板反应的影响。通过用沙利度胺预处理动物，足底内 (i.pl.) 注射角叉菜胶或缓激肽的痛觉过敏反应以剂量依赖性方式受到抑制，角叉菜胶或缓激肽通过刺激 TNF-α 释放而发挥作用，但不响应 TNF-α 或前列腺素 E-2。通过用沙利度胺预处理小鼠，腹膜内（i.p.）注射酵母聚糖或乙酸诱导的伤害性扭体反应也以剂量依赖性方式受到抑制。此外，沙利度胺预处理还降低了小鼠注射酵母聚糖诱导的腹膜细胞中 TNF-α mRNA 水平。沙利度胺的镇痛作用并非由于中枢作用，因为该药物在热板试验中没有作用。沙利度胺能够抑制大鼠炎症性痛觉过敏和小鼠扭动伤害性反应的证明表明，这些镇痛作用似乎是抑制 TNF-α 产生的结果。并指出需要研究使用沙利度胺治疗经典非麻醉镇痛药难治性疼痛的可能性。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Tumor necrosis factor alpha (TNF-alpha) may have a pivotal role in the genesis of mechanical inflammatory hyperalgesia in rats and in the nociceptive writhing response in mice. Thalidomide has been shown to selectively inhibit TNF-alpha production. We therefore investigated the effect of thalidomide on these responses as well as on the hot plate response in mice. Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin or bradykinin, which act by stimulating TNF-alpha release, but not responses to TNF-alpha or prostaglandin E-2, were inhibited in a dose-dependent manner by pretreatment of the animals with thalidomide. The nociceptive writhing responses induced by intraperitoneal (i.p.) injections of zymosan or acetic acid were also inhibited in a dose-dependent manner by pretreatment of mice with thalidomide. Moreover, the thalidomide pretreatment also reduced the TNF-alpha mRNA levels in the peritoneal cells induced by injection of zymosan in mice. The analgesic effect of thalidomide is not due to a central effect, since the drug had no effect in the hot plate test. The demonstration that thalidomide is able to inhibit inflammatory hyperalgesia in rats and the writhing nociceptive response in mice suggests that these analgesic effects seem to be a consequence of the inhibition of TNF-alpha production. and indicates the need for investigations on the possibility of the use of thalidomide for the treatment of pain refractory to classical non-narcotic analgesics. (C) 2000 Elsevier Science B.V. All rights reserved.