Lab of Neuropharmacology and Toxicology, Shanghai University, Shanghai, 200444, PR China.
Eur J Pharmacol. 2009 Nov 25;623(1-3):52-64. doi: 10.1016/j.ejphar.2009.09.028. Epub 2009 Sep 24.
The present study investigated whether spinal astrocyte and microglia were activated in Buthus martensi Karch (BmK) venom-induced rat pain-related behaviors. The results showed that glial fibrillary acidic protein (GFAP) immunoreactivity indicative astrocyte activation in bilateral spinal cord started to increase by day 3, peaked at day 7 and gradually reversed at day 14 following intraplantar injection of BmK venom. Western blotting analysis confirmed GFAP expression was up-regulated by BmK venom. In contrast, bilateral spinal increase of OX-42 immunoreactivity indicative of microglial activation began at 4h peaked at day 1 and gradually reversed by days 3 to 7 after the administration of BmK venom. Pretreatment with either intrathecal injection of fluorocitrate or intraperitonial injection of minocycline, and two glial activation inhibitors, suppressed the spontaneous nociceptive responses, and prevented the primary thermal and bilateral mechanical hyperalgesia induced by BmK venom. The post-treatment with fluorocitrate or minocycline could not affect the mechanical hyperalgesia. Moreover, minocycline partially inhibited BmK venom-induced spinal c-Fos expression but lack of effects on BmK venom-induced paw edema. Taken together, the current study demonstrated that spinal astrocyte and microglial activation may contribute to BmK venom-induced rat pain-related behaviors. Thus, spinal glia may represent novel targets for effective treatment of pain syndrome associated with scorpion envenomation.
本研究探讨了鞘蛛毒素(BmK)诱导的大鼠疼痛相关行为是否激活了脊髓星形胶质细胞和小胶质细胞。结果表明,双侧脊髓内 GFAP 免疫反应性星形胶质细胞激活自 BmK 毒液注射后第 3 天开始增加,第 7 天达到高峰,第 14 天逐渐逆转。Western blot 分析证实 BmK 毒液上调了 GFAP 表达。相比之下,双侧脊髓 OX-42 免疫反应性增加表明小胶质细胞激活始于 4 小时,第 1 天达到高峰,在 BmK 毒液给药后第 3 至 7 天逐渐逆转。鞘内注射氟柠檬酸或腹腔内注射米诺环素,以及两种胶质细胞激活抑制剂,可抑制自发性痛觉反应,并预防 BmK 毒液引起的原发性热痛觉过敏和双侧机械性痛觉过敏。氟柠檬酸或米诺环素的后期治疗不能影响机械性痛觉过敏。此外,米诺环素部分抑制了 BmK 毒液诱导的脊髓 c-Fos 表达,但对 BmK 毒液诱导的爪肿胀没有影响。总之,本研究表明,脊髓星形胶质细胞和小胶质细胞的激活可能参与了 BmK 毒液诱导的大鼠疼痛相关行为。因此,脊髓胶质细胞可能是治疗与蝎毒中毒相关的疼痛综合征的新靶点。