Mesenchymal Stem Cells Transplantation for Neuropathic Pain Induced By Peripheral Nerve Injury in Animal Models: A Systematic Review.

Neuropathic pain is defined as a lesion or disease of the somatosensory system, currently remaining a challenging condition to treat. Mesenchymal stem cells (MSCs) transplantation is emerging as a promising strategy to alleviate the neuropathic pain conditions induced by peripheral nerve injury. The aim of this systematic review was to assess the efficacy and safety of MSCs transplantation in neuropathic pain induced by peripheral nerve injury in controlled animal studies, and thus to yield evidence-based decision making. Following the PRISMA guidelines, PubMed, Cochrane Central Library, Embase, and CINAHL were searched for preclinical controlled animal studies from the inception to April 16, 2020. Seventeen studies are included in this review. Substantial heterogeneity is observed regarding the animal's species, models of neuropathic pain, regimen of MSCs transplantation, and outcome of measures across the included studies. Both mechanical allodynia and thermal hyperalgesia could be significantly attenuated by transplanted MSCs. The MSCs-elicited analgesic effect is independent of the type of MSCs, time of administration, and route of delivery, and is efficiently enhanced by genetic transfection with fibroblast growth factor, proenkephalin, and glial cell line-derived neurotrophic factor. The migration of MSCs after intrathecal or intravenous injection has been shown to be directed toward the surface of dorsal spinal cord or dorsal root ganglions on the ipsilateral side of injury. No adverse effects have been reported. The accumulating evidence demonstrates the therapeutic effect of MSCs-based cell therapy on prevention and alleviation of the neuropathic pain induced by peripheral nerve injury in rat or mouse models. The robust preclinical studies are deserved to optimize the regimen of MSCs transplantation and to promote the translation of the MSCs-based therapy into clinical studies.