Off-Label Applications of Epidural Spinal Cord Stimulation: A Scoping Review

Area of Science:

• Neuromodulation
• Rehabilitation Medicine
• Cardiovascular Research

Background:

• Epidural spinal cord stimulation (SCS) is an established treatment for chronic pain.
• Emerging research explores SCS for conditions beyond neuropathic pain, including cardiovascular, neurological, and rehabilitation applications.

Purpose of the Study:

• To conduct a scoping review of clinical literature on epidural SCS for non-neuropathic pain applications.
• To map publication trends, summarize outcomes, and synthesize proposed mechanisms of action.

Main Methods:

• Searched MEDLINE, EMBASE, CENTRAL, and WHO trials registry for English human studies.
• Included full-text studies of epidural SCS for applications beyond chronic neuropathic pain.
• Performed duplicate screening and extraction, with adjudication by a third reviewer; assessed risk of bias for RCTs and prospective studies.

Main Results:

• Included 221 studies (1976-2025) covering vascular, cardiovascular, motor function/rehabilitation post-SCI, neurodegenerative disorders, and disorders of consciousness.
• Evidence was most consistent for refractory angina and spasticity; findings for critical limb ischemia, disorders of consciousness, and SCI rehabilitation were mixed or early-phase.
• Proposed mechanisms commonly involved autonomic/microvascular modulation and altered spinal network excitability, but were rarely tested prospectively.

Conclusions:

• Epidural SCS has diverse applications beyond chronic neuropathic pain, but the strength of evidence is uneven.
• Future research requires hypothesis-driven trials with standardized outcomes and validated predictors for patient selection.
• Comparative effectiveness studies are needed to define SCS's evolving therapeutic role.