Treating peripheral nerve injury-induced spinal cord degeneration and neuropathic pain with peripherally administrated stem cells

Abstract

Peripheral nerve injury (PNI) causes sensory and motor deficits as well as neuropathic pain, which seriously impacts patient quality of life (Jiang et al., 2017). Morphological and molecular changes in the spinal cord and dorsal root ganglia (DRG), such as neuronal cell death, nerve fiber degeneration, and glial activation, are strongly associated with PNI-induced pathological syndromes, such as sensitization and abnormal responses to peripheral stimuli and dysregulation of spinal cord circuitry (Calvo and Bennett, 2012; Duraikannu et al., 2019; Zhang et al., 2021). To date, most therapeutic strategies for functional recovery after PNI target the peripheral nerve directly, while only a few treatments target PNI-induced pathological changes in the spinal cord, such as preventing apoptosis-induced neuronal death and inhibiting glial responses. This in part explains why despite continual improvements in therapeutic strategies of PNI over the last few decades, clinical outcomes after PNI remain unsatisfactory, such as suffering from chronic pain. Therefore, there is an urgent need for new therapeutic strategies. Considering the anatomical location of the cell bodies of the peripheral nerve in the spinal cord and DRG and the functional integration between the peripheral and central nervous system, therapeutic approaches targeting PNI-induced spinal cord lesions may benefit post-PNI outcomes. Recently, an in vivo study of the treatment of PNI-induced spinal cord pathological changes through peripheral administration of neural crest stem cells (NCSCs) (2 × 106 in a nerve conduit) achieved favorable outcomes after PNI, such as neuropathic pain relief and locomotor function improvements (Zhang et al., 2021). This preclinical study provides insight into the therapeutic potential of a new approach to PNI by targeting PNI-induced spinal cord lesions through peripheral administration of NCSCs, instead of intrathecal injection or transplantation to the injured dorsal root, which holds the potential to translate into clinical practice in the future.