Ultra Low Frequency Neuromodulation Directly Inhibits Pain Signaling Without Affecting Normal Sensory Function

Introduction: Chronic low back pain (CLBP) continues to be a prevalent and disabling condition worldwide. Spinal cord stimulation (SCS), commercially available since the 1980s, is effective for neuropathic pain conditions; however, many patients with CLBP have predominant somatic or nociceptive pain and are not well treated with current SCS devices. Early data for Ultra Low Frequency (ULF™) SCS suggest a novel mechanism of action that directly inhibits neural activity(1). This first-in-human study evaluated the safety and effectiveness of ULF neuromodulation.

Methods: This prospective, single-arm, multicenter clinical trial enrolled subjects with CLBP, with or without leg pain, and treated them with ULF SCS (Presidio Medical, San Mateo, CA USA).
Eligible participants had CLBP rated a minimum of 60 out of 100mm on a visual analog scale (VAS) with symptoms refractory to conservative therapy for at least 3 months and were medically suitable to undergo SCS procedures. Neurological examination of lower limb sensation, motor strength, and reflexes was performed at Baseline, post-implant prior to therapy initiation, and at 1- and 3-month follow-up visits. Participants were assessed for intensity of both neuropathic and non-neuropathic pain by the Short-Form McGill Pain Questionnaire (SF-MPQ-2) at Baseline and 1- and 3-month follow-up visits. Statistical significance was assessed as two-tailed p-value < 0.05 with a paired t-test.

Results: A total of 50 participants received ULF SCS device implants, including 29 (58%) females and 21 (42%) males. The median age was 64.6 years (range:27.5-91.3) with average BMI of 30.2kg/m2 (SD:5.2) and an average 21-year history of CLBP (range:1-70). Pain was characterized by clinical evaluation as predominantly nociceptive for 28 (56%) participants, predominantly neuropathic for 6 (12%), and the remaining 16 (32%) had significant contributions of each. The Total SF-MPQ-2 score at Baseline was 3.8 and improved to 1.1 at 3 months (p < 0.05). Significant improvement was observed across all SF-MPQ-2 subdomains: Continuous, Intermittent, Neuropathic, and Affective descriptors (p < 0.05 for each). There were no instances of deterioration in motor strength, sensory function, or reflexes on neurological examination.

Conclusion: Nociceptive CLBP has long been undertreated and there is a dearth of SCS research targeting this patient group(2). Thus, treatment guideline recommendations and payer coverage specifically endorse SCS to treat neuropathic conditions and not predominant nociceptive pain. While participants demonstrated improvement across both neuropathic and non-neuropathic pain descriptors, sensory function remained intact. ULF neuromodulation safely and effectively treats CLBP via a unique mechanism of neural inhibition that blocks chronic pain signaling without affecting normal sensation.