鸡矢藤注射液和野木瓜注射液对大鼠足底皮下化学组织损伤诱致自发痛、痛敏和炎症的作用

研究市售中药制剂鸡矢藤注射液和野木瓜注射液有无抗伤害及抗炎作用。采用两种持续性痛动物实验模型——蜜蜂毒(bee venom,BV)模型和福尔马林(formalin,F)模型,评价鸡矢藤注射液和野木瓜注射液系统给药对持续性自发痛反应、原发性热和机械痛敏及炎症反应的作用效果。成年清醒大鼠足底皮下注射BV(0．2％,50μl)不仅可诱发注射侧长达1h以上的、持续的、单相性的自发痛反应(其表现为自发缩足反射行为)和之后出现的持续3—4d的原发性热和机械痛敏现象,而且注射爪出现明显的红、肿等炎症反应。皮下注射F(2．5％,50μl)则产生双相性自发痛反应。与盐水组比较,致痛前系统给予0．32、1．6和9．0ml／kg三个剂量的500％鸡矢藤注射液或250％野木瓜注射液,对BV或F诱致的1h自发缩足反射次数具有剂量依赖性抑制作用;致痛5min后分别给予鸡矢藤或野木瓜注射液对BV或F诱发的自发痛反应也产生显著的抑制作用。然而,致痛前或致痛后静脉注射鸡矢藤注射液或野木瓜注射液对BV诱致的原发性热／机械痛敏及炎症反应均无明显的抑制作用。纳洛酮(一种非选择性的阿片受体拮抗剂)不能翻转鸡矢藤或野木瓜注射液对BV产生的自发痛反应的镇痛作用,提示其镇痛作用不是由内源性阿片受体介导。本研究结果证实鸡矢藤或野木瓜注射液能预防和缓解临床持续性自发痛,但是对原发性热／机械痛敏及炎症反应均无抗伤害效应和抗炎作用。在中药镇痛抗炎有效成分的筛选和评价中,BV模型是一个理想的实验动物模型。

Effects of intravenous Injections Paederiae and Stauntonia on spontaneous pain, hyperalgesia and inflammation induced by cutaneous chemical tissue injury in the rat

To study whether commercial traditional Chinese medicinal preparations Injection Paederiae (IP) or Injection Stauntonia (IS) has anti-nociceptive and/or anti-inflammatory effects, we used two persistent pain models (bee venom and formalin test) to evaluate the systemic effects of IP or IS on the chemical tissue injury-induced persistent spontaneous pain-related responses (PSPR), primary thermal/mechanical hyperalgesia and inflammation in conscious rats. Injection of bee venom (BV, 0.1 mg, 50 microl) into the plantar surface of one hind paw resulted in not only a 1-h monophasic PSPR such as flinching reflex in the injected paw and a subsequent period of 3-4 days primary heat and mechanical hyperalgesia, but also a marked sign of inflammation, including redness and swelling of the plantar surface in the injected paw. Intraplantar injection of formalin produced two phases of PSPR as reported previously. Systemic pre-treatment with three doses of IP (0.32, 1.6 and 9.0 ml/kg, 500%) or IS (0.32, 1.6 and 9.0 ml/kg, 250%) produced a dose-dependent suppression of the BV- or formalin-induced flinching reflex of 1 h time course as compared with the saline control group. Post-treatment with IP or IS 5 min after BV injection also produced a significant suppression of the flinching reflex in both BV test and formalin test respectively, as compared with the control group. However, neither pre- nor post-treatment with IP or IS produced any significantly suppressive effect on the BV-induced primary heat and mechanical hyperalgesia and inflammation. The analgesia produced by IP or IS was not mediated by the endogenous opioid receptors since naloxone, a non-selective opioid receptor antagonist, had no reversal effect on the IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest that IP or IS might prevent and relieve clinical persistent spontaneous pain, but without any anti-nociceptive and anti-inflammatory effects on the primary heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses. The BV test might be a useful model of pain to evaluate and screen anti-nociceptive and anti-inflammatory effects of certain compounds of the Chinese medicinal herbs on the pathological origins of pain.