Department of Anesthesiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Brain Res. 2012 Feb 3;1436:122-9. doi: 10.1016/j.brainres.2011.11.051. Epub 2011 Dec 4.
Triptolide is a potent immunosuppressive drug capable of inhibiting T cell activation and proliferation. Recent studies show that T cells play an important role in neuropathic pain following nerve injury in rats. In this study, we investigated the effect of triptolide on T cell activation and development of neuropathic pain. Neuropathic pain by chronic constriction injury (CCI) was induced by loose ligation of the sciatic nerve in Sprague-Dawley rats. Triptolide (5 or 10 μg/kg) or vehicle (DMSO) was administered intrathecally after surgery for 7 days (n=8 per group). The right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before and after the surgery (days 0 to 7). NF-κB activation and pro-inflammatory cytokine (TNF-α and IL-2) expression were determined by ELISA, Western blot, and real time-PCR. CCI of the sciatic nerve induced mechanical allodynia and thermal hyperalgesia in these rats. Intrathecal triptolide (5 and 10 μg/kg) suppressed the development of allodynia and thermal hyperalgesia. It also inhibited CCI-induced inflammation and T cell activation, by decreasing spinal cord TNF-α, IL-2 and NF-κB p65 levels. Motor dysfunction was not observed after triptolide treatment. In the present study, we demonstrated the suppressive effect of triptolide on the development of neuropathic pain. Therefore, triptolide could be a promising immunosuppressive agent in the treatment of neuropathic pain. Further studies are required to examine the safety of intrathecal triptolide for clinical application.
雷公藤红素是一种强效的免疫抑制剂，能够抑制 T 细胞的激活和增殖。最近的研究表明，T 细胞在大鼠神经损伤后的神经病理性疼痛中发挥重要作用。在本研究中，我们研究了雷公藤红素对 T 细胞激活和神经病理性疼痛发展的影响。通过坐骨神经慢性缩窄性损伤（CCI）在 Sprague-Dawley 大鼠中诱导神经病理性疼痛。手术后，用雷公藤红素（5 或 10μg/kg）或载体（DMSO）鞘内给药 7 天（每组 8 只）。在手术前后（第 0 天至第 7 天）测定右后爪对 von Frey 细丝刺激的退缩阈值和对辐射热的退缩潜伏期。通过 ELISA、Western blot 和实时 PCR 测定 NF-κB 激活和促炎细胞因子（TNF-α和 IL-2）表达。CCI 引起这些大鼠的机械性痛觉过敏和热痛觉过敏。鞘内给予雷公藤红素（5 和 10μg/kg）可抑制痛觉过敏和热痛觉过敏的发展。它还通过降低脊髓 TNF-α、IL-2 和 NF-κB p65 水平抑制 CCI 诱导的炎症和 T 细胞激活。雷公藤红素治疗后未观察到运动功能障碍。在本研究中，我们证明了雷公藤红素对神经病理性疼痛发展的抑制作用。因此，雷公藤红素可能是治疗神经病理性疼痛的一种有前途的免疫抑制剂。需要进一步研究鞘内给予雷公藤红素的安全性，以用于临床应用。
