Polydopamine-Coated Poly( <scp>l</scp> -lactide) Nanofibers with Controlled Release of IL-10 for Effective Management of Peripheral and Central Neuropathic Pain in Rats

Managing neuropathic pain is challenging due to the complex pathogenetic mechanisms and limited available drugs and therapeutic options. Innovative nanofiber systems offer a novel method to effectively administer therapeutic cytokines, drugs, or small molecule compounds to achieve better relief of neuropathic pain. Here, we report a novel nanofiber with controlled release of IL-10 for implantation into ligated nerve roots and hemisection-injured spinal cords to exert anti-inflammatory effects and attenuate neuropathic pain. An electrospun poly(l-lactide) (PLLA) nanofiber was modified by a polydopamine (PDA) coating, and this nanofiber demonstrated sustained release of IL-10 in vitro. We showed that L5 spinal nerve ligation and T13 spinal cord hemisection induced peripheral and below-level central neuropathic pain in rats, along with the development of neuroinflammation. Spinal IL-10 was also markedly changed after spinal nerve ligation (SNL) or spinal cord injury (SCI), especially in the spinal dorsal horn. Rats were treated postsurgically with IL-10 that was loaded on PDA@PLLA nanofibers as an implantable cytokine delivery system. IL-10 levels were significantly upregulated after the implantation of PDA@PLLA nanofibers in SNL and SCI rats. We further demonstrated that the implantation could inhibit glial activation and neuronal excitability in vivo, along with suppressing the expression levels of pro-inflammatory cytokines. Most importantly, IL-10-loaded PDA@PLLA nanofiber treatment attenuated the development and maintenance of peripheral and central neuropathic pain. Together, the combination of IL-10 and PDA@PLLA nanofibers provides a novel implantable delivery system for treating neuroinflammatory conditions and may emerge as a promising agent to prevent chronic neuropathic pain.