Abstract
INTRODUCTION: With the advancement of technology, peripheral nerve stimulation (PNS) has been increasingly used to treat various chronic pain conditions. Its origin is based on the gate control theory postulated by Wall and Melzack in 1965. However, the exact mechanism behind PNS' analgesic effect is largely unknown. In this article, we performed a comprehensive literature review to overview the PNS mechanism of action. DESIGN: A comprehensive literature review on the mechanism of PNS in chronic pain. METHODS: Comprehensive review of the available literature on the mechanism of PNS in chronic pain. Data were derived from database searches of PubMed, Scopus, and the Cochrane Library and manual searches of bibliographies and known primary or review articles. RESULTS: Animal, human, and imaging studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and involvement of the cortical and subcortical areas. CONCLUSIONS: Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the mechanism of PNS can help guide stimulation approaches and parameters to optimize the use of PNS.