Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3336-3348.doi: 10.4103/NRR.NRR-D-25-00553

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Spinal cord stimulation: emerging strategy for chronic pain relief after spinal cord injury

Qiwen Wang1, #, Ying Zhang1, 2, #, Huifeng Zhang1, 2, Zhonghai Li1, *   

  1. 1Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 
    2Dalian Medical University, Dalian, Liaoning Province, China
  • Online:2026-08-18 Published:2026-04-23
  • Contact: Zhonghai Li, PhD, lizhonghaispine@126.com.
  • Supported by:
    This work was supported by Key Tackling Project of the Education Department of Liaoning Province, No. 2024C011; and the Medical-Industrial Joint Innovation Funding Project of the First Hospital of Dalian Medical University and Dalian Institute of Chemical Physics, No. DMU-1&DICP UN202311 (both to ZL).

Abstract: Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury. This pain can manifest as burning, stinging, or sensations similar to electric shocks. Recent studies have shown that spinal cord stimulation is an effective way to treat chronic pain after spinal cord injury. The purpose of this review is to introduce the technique of spinal cord stimulation, the clinical manifestations of spinal cord injury, and the role of spinal cord stimulation in the treatment of spinal cord injury. The mechanism and clinical application of spinal cord stimulation in the treatment of pain after spinal cord injury are discussed. The mechanism of spinal cord stimulation primarily involves three aspects: neuromodulation, neurochemical regulation, and anti-inflammatory effects, along with nerve repair. In terms of neuromodulation, spinal cord stimulation is based on the gate control theory of pain. It activates large-diameter Aβ nerve fibers to promote the release of inhibitory neurotransmitters by gamma-aminobutyric acidergic inhibitory interneurons in the spinal cord, thereby blocking the transmission of pain signals from small-diameter C fibers. Neurochemical studies indicate that spinal cord stimulation can regulate the balance of neurotransmitters within the spinal cord, increasing the release of inhibitory neurotransmitters such as gamma-aminobutyric acid, serotonin, and acetylcholine while reducing the levels of excitatory neurotransmitters. Additionally, spinal cord stimulation exhibits significant anti-inflammatory and neuroprotective effects, downregulating pro-inflammatory factor levels, upregulating anti-inflammatory factor expression, alleviating neuroinflammatory responses, and repairing damaged neural circuits by promoting the secretion of neurotrophic factors and axonal regeneration. Spinal cord stimulation have demonstrated remarkable efficacy in the clinical treatment of pain after spinal cord injury, but there are still limitations such as small sample size and high heterogeneity in clinical studies, as well as insufficient long-term efficacy data. Future research should conduct multi-center large-sample randomized controlled trials, and establish long-term follow-up mechanisms to improve evidence-based medical evidence.

Key words: chronic pain, electric stimulation therapy, GABAergic neurons, nerve regeneration, neuroinflammatory diseases, neuronal plasticity, neuropathic pain, neuroprotection, pain management, spinal cord injuries, spinal cord stimulation