Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Republic of Korea.
Brain Res Bull. 2011 Nov 25;86(5-6):412-21. doi: 10.1016/j.brainresbull.2011.08.012. Epub 2011 Aug 26.
Spinal astrocytes have emerged as important mechanistic contributors to pathological and chronic pain. Recently, we have demonstrated that injection of diluted bee venom (DBV) into the Zusanli (ST36) acupoint produces a potent anti-nociceptive effect via the activation of spinal alpha-2 adrenoceptors. However, it is unclear if this anti-nociceptive effect is associated with alterations in spinal astrocytes. Thus, the present study was designed to determine: (1) whether DBV's anti-nociceptive effect in the formalin test involves suppression of spinal astrocyte activation; (2) whether DBV-induced astrocyte inhibition is mediated by spinal alpha-2 adrenoceptors; and (3) whether this glial modulation is potentiated by intrathecal administration of the glial metabolic inhibitor, fluorocitrate (FC) in combination with DBV injection. DBV was injected directly into the ST36 acupoint, and spinal expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), was assessed together with effects on formalin-induced nociception. DBV treatment reduced pain responses in the late phase of the formalin test and significantly blocked the formalin-evoked increase in spinal GFAP expression. These effects of DBV were prevented by intrathecal pretreatment with selective alpha-2A and alpha-2C adrenoceptor antagonists. Moreover, low dose intrathecal injection of FC in conjunction with low dose DBV injection into the ST36 acupoint synergistically suppressed pain responses and GFAP expression. These results demonstrate that DBV stimulation of the ST36 acupoint inhibits the formalin-induced activation of spinal astrocytes and nociceptive behaviors in this inflammatory pain model and this inhibition is associated with the activation of spinal alpha-2 adrenoceptors.
脊髓星形胶质细胞已成为病理性和慢性疼痛的重要机制贡献者。最近，我们已经证明，将稀释的蜂毒（DBV）注射到足三里（ST36）穴位中，通过激活脊髓α-2肾上腺素能受体产生强大的抗伤害作用。然而，尚不清楚这种抗伤害作用是否与脊髓星形胶质细胞的改变有关。因此，本研究旨在确定：（1）DBV 在福尔马林试验中的抗伤害作用是否涉及抑制脊髓星形胶质细胞的激活；（2）DBV 诱导的星形胶质细胞抑制是否由脊髓 α-2 肾上腺素能受体介导；（3）这种神经胶质调节是否通过鞘内给予神经胶质代谢抑制剂氟柠檬酸（FC）与 DBV 注射联合增强。DBV 直接注射到 ST36 穴位，评估脊髓星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达，并评估其对福尔马林诱导的疼痛的影响。DBV 处理减少了福尔马林试验后期的疼痛反应，并显著阻断了福尔马林诱发的脊髓 GFAP 表达增加。DBV 的这些作用被鞘内预先给予选择性 α-2A 和 α-2C 肾上腺素能受体拮抗剂所阻止。此外，低剂量鞘内注射 FC 与低剂量 DBV 注射到 ST36 穴位联合使用，协同抑制疼痛反应和 GFAP 表达。这些结果表明，DBV 刺激 ST36 穴位抑制福尔马林诱导的脊髓星形胶质细胞激活和这种炎症性疼痛模型中的伤害性行为，这种抑制与脊髓 α-2 肾上腺素能受体的激活有关。
