Intrathecal administration of human bone marrow mesenchymal stem cells genetically modified with human proenkephalin gene decrease nociceptive pain in neuropathic rats.

Background: Mesenchymal stem cell (MSC) has been one of the potential tools in neuropathic pain therapy; however, the augmented efficacy may be expected when they are modified with human proenkephalin (hPPE) gene. In the current study, the antinociceptive effect of human bone marrow stem cells (hBMSCs) engineered with hPPE gene (hPPE-hBMSCs) on sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain in rats was investigated. Methods: Primary-cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 x 10(6)) were then intrathecally injected into a rat model of CCI. Paw mechanical withdrawal threshold and paw withdrawal thermal latency were measured before and after CCI surgery. The effects of hPPE gene transfer on hBMSCs bioactivity were analyzed invitro and invivo. Results: No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved paw mechanical withdrawal threshold and paw thermal withdrawal latency values on the ipsilateral side of rats with CCI from day 9 post-surgery, and the analgesic effect was reversed by naloxone. Leucine-enkephalin (L-EK) secretion was augmented in the hPPE-engineered hBMSC group. Conclusions: The intrathecal administration of BMSCs modified with hPPE gene can effectively relieve pain caused by chronic constriction injury in rats and might be a potentially therapeutic tool for neuropathic pain in humans.