Peripheral Nerve Stimulation for Chronic Pain: Mechanisms, Evidence, and Clinical Integration

Peripheral nerve stimulation (PNS) represents one of the oldest and yet most rapidly evolving neuromodulation strategies for the management of chronic pain. Although the conceptual foundations of nerve stimulation can be traced to the early nineteenth century, rigorous clinical investigation began only in 1976, when Campbell and colleagues published the first clinical series on PNS for pain management.[1] In the decades since, PNS has matured from an experimental curiosity into a guideline-endorsed therapeutic modality, with formal recommendations now issued by the American Society of Pain and Neuroscience (ASPN) and the American Society of Interventional Pain Physicians (ASIPP).[6][7] Contemporary practice recognizes two fundamentally distinct paradigms: permanent implantation, in which analgesia depends on continuous device operation, and temporary 60-day percutaneous therapy, in which a lead is withdrawn after a finite treatment course and relief is expected to persist through reconditioning of central pain processing.[20] This distinction carries profound implications for patient selection, cost, informed consent, and the interpretation of published outcomes. The mechanistic basis of electrical PNS rests largely on the gate control theory, supplemented by GABA-mediated inhibition of wide-dynamic-range hyperexcitability and stimulation-induced release of serotonin, adenosine, and noradrenaline.[16][17][18] Clinical evidence supports PNS across a broad spectrum of focal pain states, including postamputation pain, occipital neuralgia, migraine, sacroiliac joint dysfunction, knee pain, shoulder impingement, upper extremity neuropathic pain, and axial low back pain.[21][22][23][24][25][26][29][30][31][33][34] The strongest controlled evidence derives from randomized, double-blind, placebo-controlled trials in postamputation pain, where an eight-week course of stimulation produced durable reductions in both residual-limb and phantom-limb pain that persisted long after lead removal.[8][31] A 2025 systematic review and meta-analysis assigned temporary 60-day PNS a fair (level III) evidence grade with moderate certainty and a moderate strength of recommendation, while noting that evidence for permanently implanted systems remains comparatively limited.[8] Procedural safety is favorable, though infection, lead migration, lead fracture with retained fragments, skin erosion, and device malfunction remain recognized concerns.[38][39][40] This review synthesizes the anatomical, physiological, technical, and clinical dimensions of PNS, situates the therapy within the broader neuromodulation landscape, and identifies the evidence gaps that must be addressed before PNS can be fully integrated into routine interventional pain practice.