Intrathecal administration of triptolide, a T lymphocyte inhibitor, attenuates chronic constriction injury-induced neuropathic pain in rats

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 mu g/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-kappa B activation and pro-inflammatory cytokine (TNF-alpha 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 mu g/kg) suppressed the development of allodynia and thermal hyperalgesia. It also inhibited CCI-induced inflammation and T cell activation, by decreasing spinal cord TNF-alpha, IL-2 and NF-kappa B 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. (C) 2011 Elsevier B.V. All rights reserved.