Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats

Abstract Aims To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. Main methods We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20 mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Na v 1.3), 1.7 (Na v 1.7), and 1.8 (Na v 1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Key findings Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA + poly(lactic-co-glycolic acid) (PLGA) + stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Significance Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response.