Authors: Usman et al.
Cureus 17(8): e90434. doi:10.7759/cureus.90434, August 18, 2025
Summary
This PRISMA-guided systematic review synthesized seven rodent studies that examined both spinal and supraspinal mechanisms of spinal cord stimulation (SCS) in neuropathic pain models. Across tonic, burst, and sub-perception paradigms, SCS restored dorsal-horn inhibitory tone (enhanced GABA/glycine signaling, reduced wide-dynamic-range neuron activity), dampened MAPK and microglial activation, and simultaneously recruited brainstem pain-control centers (periaqueductal gray, rostroventromedial medulla, locus coeruleus). Functional readouts showed normalization of aberrant cortical oscillations; lesion/pharmacologic blockade experiments indicated that disrupting either ascending or descending pathways roughly halves analgesic efficacy, supporting a bidirectional feedback loop. fMRI suggested waveform-specific supraspinal engagement (burst vs. tonic). The authors propose a unified spinal–supraspinal model to guide future electrode placement and waveform design, while noting translational limits from preclinical heterogeneity and moderate risk of bias.
What You Should Know
• SCS analgesia arises from an integrated loop: segmental dorsal-horn inhibition plus supraspinal recruitment and descending control.
• Blocking ascending or descending pathways reduces efficacy by about half, underscoring the need to engage both.
• Waveform matters: burst and tonic stimulation differentially engage sensory vs. affective networks on fMRI.
• Mechanistic signals include boosted GABA/glycine tone, reduced dorsal-horn hyperexcitability, and tempered neuroinflammation.
• Translational takeaway: parameter selection (lead location, frequency, waveform) should target both spinal gating and supraspinal modulation.
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