A pilot study of novel ultrahigh-frequency dorsal root ganglia stimulation for chronic lower limb pain: Focusing on safety and feasibility

Objectives: This single-arm, open-label, single-center observational pilot study assessed the safety and efficacy of ultrahigh-frequency dorsal root ganglia (UHF-DRG) stimulation in patients with chronic leg pain with or without low back pain. Such high-frequency electrostimulation had not been conducted in the human central nervous system previously.

Materials and methods: The primary objective was to evaluate the safety of UHF-DRG stimulation (2 Hz pulses with 50 msec pulse-width and 500 kHz intrapulse sine waves, 5-min duration per stimulation) by identifying incident adverse events (AE) and severe adverse events (SAE) during the trial. The secondary objectives included assessment of pain reduction using a numerical rating score (NRS), presence of paraesthesia, and changes in four pain medications (weak opioids, anticonvulsants, antidepressants, and non-steroid-anti-inflammatory drugs). One DRG lead was implanted for one day then removed, and the patients received maximal three times of UHF stimulation in total.

Results: The study focused on ten cases. Two of them did not complete the study due to difficulty of lead implantation. There was no SAE in this trial. Among the ten cases, AEs occurred in eight, three experienced injection-related local pain and one of them had a post-dural-puncture headache, others had symptoms un-related to implantation procedure or UHF stimulation. The average NRS was reduced from 6.4 ± 1.1 at baseline to 2.9 ± 1.1 on the second-day post-implantation, and it was striking that the NRS was maintained at 3.6 ± 2.8 until 2 days after lead removal. The results showed a trend of lower frequency in medication use for all types of analgesics.

Conclusions: In this first-in-human pilot study, we discovered that intermittent pulsed UHF-DRG stimulations ameliorated chronic lower limb pain for an extended period in humans. Our finding opens up a new neuromodulatory concept and may initiate a novel paradigm for treating intractable pain.