Aug 2026· Journal of Clinical Medicine· Vol 15, pp. 6574· 0 citations· 73 references
TL;DR
Future progress in SCS will likely depend on artificial intelligence, remote monitoring, biomarker-guided programming, and integration with multidisciplinary chronic pain care.
Abstract
Chronic pain continues to be a major global health burden and is frequently refractory to conventional pharmacologic and conservative therapies. Spinal cord stimulation (SCS) has emerged as an important neuromodulatory treatment for selected patients with chronic neuropathic and mixed pain syndromes. Since its introduction in the 1960s, SCS has evolved from paresthesia-based tonic stimulation into more adaptive and personalized neuromodulation. This review summarizes the current evidence regarding the mechanisms, clinical applications, technological advances, and future directions of SCS therapy. Mechanistically, SCS modulates nociceptive transmission through dorsal column and dorsal horn pathways, inhibitory neurotransmitter systems, wide-dynamic-range neuronal activity, and supraspinal pain-processing networks. Technological advances have expanded available stimulation paradigms, including burst stimulation, high-frequency stimulation, closed-loop evoked compound action potential-controlled systems, and differential target multiplexed stimulation. These approaches aim to improve analgesic durability, reduce the burden of paresthesia, and address mechanisms such as neuroinflammation and neural habituation. Clinically, SCS is used for conditions including failed back surgery syndrome, complex regional pain syndrome, painful diabetic neuropathy, ischemic limb pain, and emerging non-traditional pain states. However, outcomes remain variable and are influenced by psychological readiness, pain phenotype, anatomic factors, trial response, neurophysiologic markers, and patient engagement. Complications such as lead migration, infection, implantable pulse generator malfunction, and loss of efficacy remain important considerations. Future progress in SCS will likely depend on artificial intelligence, remote monitoring, biomarker-guided programming, and integration with multidisciplinary chronic pain care.
Its role is comparatively well supported in selected chronic neuropathic pain populations, particularly chronic back and leg pain after spinal surgery and painful diabetic neuropathy, and applications in diabetic foot complications, spinal cord injury, and disorders of consciousness are supported mainly by small, heterogeneous, or uncontrolled studies.
Mengyun He, Yu Tan, Ze He et al.· Frontiers in Neurology· 0 citations
Spinal cord stimulation (SCS) is a widely used neuromodulatory therapy for chronic neuropathic pain, yet the cellular and molecular mechanisms underlying its clinical efficacy remain incompletely understood. This review synthesizes current literature on the neurophysiology of pain transmission and the mechanistic basis of major SCS paradigms (tonic, high-frequency, burst, and closed-loop stimulation), highlighting how each modality engages distinct dorsal horn circuits, glial and inflammatory pathways, as well as supraspinal networks involved in the affective dimension of pain. Particular attention is given to the evoked compound action potential (ECAP) as an emerging electrophysiological biomarker that enables real-time, feedback-guided stimulation and offers insight into the biophysical determinants of dorsal column activation. We also examine preclinical and clinical evidence linking SCS to modulation of central sensitization, neuroinflammatory signaling, and autonomic regulation, while identifying persistent gaps in mechanistic understanding. Finally, we discuss future directions, including AI-assisted, personalized SCS programming and expanding indications beyond classical neuropathic pain, underscoring the need for multimodal experimental approaches to more precisely define how SCS achieves analgesia.
Milan Patel, Alison J Deng, Ameya V Belamkar et al.· International Journal of Mol...· 0 citations
ABSTRACT Introduction Chronic migraine (CM) refractory to conventional pharmacotherapy (r-CM) remains a debilitating neurological condition with limited therapeutic options. High-frequency spinal cord stimulation at 10 kilohertz (HF-SCS) has recently emerged as a distinct neuromodulatory paradigm for this patient population. Unlike traditional spinal cord stimulation, HF-SCS operates above the frequency range that generates paresthesia, thereby eliminating stimulation-induced sensation while potentially engaging unique analgesic mechanisms. Areas covered This focused narrative review synthesizes the available clinical evidence, technical considerations, and mechanistic hypotheses specifically pertaining to cervical HF-SCS for refractory chronic migraine (r-CM). The authors further provide their expert perspectives on the future of this technology as a treatment option for refractory chronic migraine. Expert opinion Current data from prospective open-label studies and retrospective case series suggest that cervical HF-SCS may reduce monthly migraine days, facilitate conversion from chronic to episodic migraine patterns in some implanted patients, and may improve headache-related disability and quality of life over at least 52 weeks of follow-up. The paresthesia-free nature of HF-SCS confers a distinct advantage for both patient tolerability and future trial design, as it permits sham-controlled methodologies that have historically been impossible with conventional neurostimulation. However, these findings remain preliminary and should be considered hypothesis-generating pending confirmation in adequately powered randomized sham-controlled trials.
Paolo Martelletti, Claudio Tana· Expert Review of Neurotherap...· 0 citations
Spinal cord stimulation (SCS) is a form of neuromodulation that delivers electrical impulses to the spinal cord, altering pain signals to provide relief from chronic pain. Since its introduction in the 1960s, SCS has primarily targeted the dorsal columns of the spinal cord. While SCS has proven effective for many neuropathic pain conditions, its limitations have driven exploration of alternative anatomical targets for electrical stimulation. Work in the 1970's suggested that ventral column spinal cord stimulation (VC-SCS) might offer superior pain relief by targeting the spinothalamic tracts (Hoppenstein, 1975). Several decades later, a study reported successful use of VC-SCS for visceral pain in 26 patients (Baranidharan et al, 2014). A recent case report demonstrated comparable outcomes between dorsal and ventrolateral SCS for post-laminectomy syndrome (van Acker and Kim, 2023). Noordin et al (2023) reported meaningful improvements in pain and function using VC-SCS in a patient with chronic visceral pain. Finally, Sheen et al (2024) demonstrated pain relief for 12 months in a patient with VC-SCS. VC-SCS represents a promising investigational approach for pain syndromes refractory to traditional dorsal column stimulation. Ongoing research should focus on refining techniques and addressing critical knowledge gaps regarding patient selection and the durability of outcomes.
Behnum A. Habibi, Chong H. Kim, Gustaf M. Van Acker· American Journal of Physical...· 0 citations
Electromagnetic neuromodulation is increasingly used as an adjunct or alternative to pharmacologic therapy for pain, with several approaches cleared for select indications and many others under active investigation. We review implanted neuromodulation approaches (intracranial and spinal), vagal neuromodulation, noninvasive central/cranial neuromodulation, peripheral neuromodulation, and hybrid/multimodal approaches, with a primary focus on chronic pain management and brief coverage of selected acute-use indications (e.g., primary headache disorders) where relevant. Beyond summarizing individual modalities, we highlight the recurring patterns that have shaped the evolution of pain neuromodulation. For each modality, we summarize putative mechanism of action, typical stimulation paradigms, and key strengths and limitations of the clinical evidence, emphasizing sources of heterogeneity that complicate cross-study comparison and translation. We conclude by outlining priorities for the field, including more rigorous trial design, standardized reporting of stimulation parameters and outcomes, and clearer indication-specific evidence to support clinical translation.
Laura Dipietro, C. Ramos-Estebanez, P. Gonzalez-Mego et al.· Frontiers in Pain Research· 0 citations
Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique widely used to modulate cortical excitability, yet its influence on spinal mechanisms remains less understood. This review synthesizes current evidence on the effects of tDCS on human spinal circuitry in both health and disease. Immediate and transient modulations of the H-reflex, a scientific analog of the stretch reflex, have been observed, suggesting short-lived alterations in spinal excitability. However, an important body of the literature also did not find any modulation of this marker. Complementary approaches, based on H-reflex conditioning paradigms, investigated in more detail specific spinal circuits that might be especially sensitive to tDCS. Such studies indicated that anodal tDCS targeted specific spinal circuits, including reciprocal inhibition, recurrent inhibition, and propriospinal pathways, with polarity- and pathway-specific effects, but not presynaptic inhibition. The effectiveness of tDCS depends on multiple factors, including polarity, montage, stimulation site, task specificity, and individual responsiveness. While variability across studies remains a major challenge, converging evidence supports the capacity of tDCS to engage spinal networks. The literature highlights that tDCS does not result in a general arousal of all spinal circuits but rather target specific structures. Future work should refine protocols, integrate multimodal strategies, and personalize interventions to fully harness spinal neuromodulation for rehabilitation and performance enhancement.
S. Grosprêtre, Markus Gruber, E. Amiri· Clinical Neurophysiology· 0 citations
