Spinal Cord Stimulation for Treating Chronic Pain: Reviewing Preclinical and Clinical Data on Paresthesia-Free High-Frequency Therapy

Abstract

Background: Traditional spinal cord stimulation (SCS) requires that paresthesia overlaps chronic painful areas. However, the new paradigm high-frequency SCS (HF-SCS) does not rely on paresthesia.

Study design: A review of preclinical and clinical studies regarding the use of paresthesia-free HF-SCS for various chronic pain states.

Methods: We reviewed available literatures on HF-SCS, including Nevro's paresthesia-free ultra high-frequency 10 kHz therapy (HF10-SCS). Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, and SCOPUS, and manual searches of the bibliographies of known primary and review articles.

Outcome measures: The primary goal is to describe the present developing conceptions of preclinical mechanisms of HF-SCS and to review clinical efficacy on paresthesia-free HF10-SCS for various chronic pain states.

Results: HF10-SCS offers a novel pain reduction tool without paresthesia for failed back surgery syndrome and chronic axial back pain. Preclinical findings indicate that potential mechanisms of action for paresthesia-free HF-SCS differ from those of traditional SCS.

Conclusions: To fully understand and utilize paresthesia-free HF-SCS, mechanistic study and translational research will be very important, with increasing collaboration between basic science and clinical communities to design better trials and optimize the therapy based on mechanistic findings from effective preclinical models and approaches. Future research in these vital areas may include preclinical and clinical components conducted in parallel to optimize the potential of this technology.

Keywords: Chronic pain; dorsal horn; frequency; paresthesia; spinal cord stimulation.

Figure 1. Schematic diagram illustrating hypothetical mechanisms for pain inhibition by paresthesia-free high-frequency (HF) spinal cord stimulation (SCS)

(A) Bipolar low-amplitude HF stimulation applied to the spinal cord surface may generate a weak, localized electric field or electrochemical disturbance (shaded area). This area may cover the superficial dorsal horn and dorsal root entry zone (DREZ) at the spinal level receiving noxious inputs (i.e., “painful” level) from dorsal root ganglion (DRG) neurons. (B) Nociceptive afferents (C-fibers, red) carrying noxious inputs mostly terminate in superficial dorsal horn, where they activate projection neurons (P) in lamina I. Large-diameter A-fibers (blue) mediating non-noxious inputs terminate in deeper laminae. Wide-dynamic range neurons (W) in deep dorsal horn also receive some C-fiber inputs through polysynaptic pathways from excitatory interneurons (E) in superficial layers. Therefore, synaptic transmission and neuronal excitability in the superficial dorsal horn may be more directly affected than deeper layers by paresthesia-free HF-SCS.