Layered Mechanisms of Spinal Cord Stimulation for Chronic Pain: A Structured Narrative Review

Spinal cord stimulation (SCS) entered pain medicine through gate-control theory, but contemporary evidence no longer supports a single-mechanism explanation. This structured narrative review examines the mechanisms proposed for SCS in chronic pain beyond a single-gate explanation.

We conducted a SANRA-informed structured narrative review using predefined database searches, auditable deduplication, and a mechanistic coding framework. The search yield and deduplication counts were treated as audit data rather than as a PRISMA-style inclusion denominator. Ninety-eight sources were cited, comprising 95 historical, mechanistic, translational, clinical-inferential, or contextual references and 3 methodological references. No quantitative synthesis was performed.

The most mature mechanistic evidence, judged by the directness of the measured endpoint, supports the modulation of spinal nociceptive processing, including dorsal horn and spinothalamic output, wide-dynamic-range neuronal activity, wind-up, and inhibitory transmitter tone. ECAP-based systems improve the measurement and stabilization of neural recruitment, but recruitment fidelity should not be equated with analgesic mechanism. Waveform-specific claims are better interpreted as parameter-dependent perturbations of excitable tissue than as mechanisms defined by label. Most dorsal horn and neurochemical evidence was obtained with paresthesia-range tonic stimulation and therefore does not transfer automatically to paresthesia-free paradigms, which constrains how much of the older mechanistic literature can be applied directly. Supraspinal imaging, psychophysical, neuroimmune, and proteomic studies extend the mechanistic field, although many remain associative, model-dependent, or endpoint-specific. Vascular and cardiac autonomic findings are reported as non-analgesic effector-system physiology rather than as evidence for mechanisms of pain relief.

SCS is better understood as a layered intervention than as a therapy governed by one explanatory mechanism. Target engagement, spinal processing, descending and supraspinal modulation, tissue-state change, and effector-system outcomes may each contribute under different conditions. Mechanistic claims should be indexed to the physiological endpoint that supports them rather than being inferred from device category or waveform terminology.