Spinal cord stimulation (SCS) is an important pain treatment modality. This study hypothesized that a novel pulsed ultrahigh-frequency spinal cord stimulation (pUHF-SCS) could safely and effectively inhibit spared nerve injury–induced neuropathic pain in rats.


Epidural pUHF-SCS (± 3V, 2-Hz pulses comprising 500-kHz biphasic sinewaves) was implanted at the thoracic vertebrae (T9 to T11). Local field brain potentials after hind paw stimulation were recorded. Analgesia was evaluated by von Frey–evoked allodynia and acetone-induced cold allodynia.


The mechanical withdrawal threshold of the injured paw was 0.91 ± 0.28 g lower than that of the sham surgery (24.9 ± 1.2 g). Applying 5-, 10-, or 20-min pUHF-SCS five times every 2 days significantly increased the paw withdrawal threshold to 13.3 ± 6.5, 18.5 ± 3.6, and 21.0 ± 2.8 g at 5 h post–SCS, respectively (P = 0.0002, < 0.0001, and < 0.0001; n = 6 per group) and to 6.1 ± 2.5, 8.2 ± 2.7, and 14.3 ± 5.9 g on the second day, respectively (P = 0.123, 0.013, and < 0.0001). Acetone-induced paw response numbers decreased from pre–SCS (41 ± 12) to 24 ± 12 and 28 ± 10 (P = 0.006 and 0.027; n = 9) at 1 and 5 h after three rounds of 20-min pUHF-SCS, respectively. The areas under the curve from the C component of the evoked potentials at the left primary somatosensory and anterior cingulate cortices were significantly decreased from pre–SCS (101.3 ± 58.3 and 86.9 ± 25.5, respectively) to 39.7 ± 40.3 and 36.3 ± 20.7 (P = 0.021, and 0.003; n = 5) at 60 min post–SCS, respectively. The intensity thresholds for pUHF-SCS to induce brain and sciatic nerve activations were much higher than the therapeutic intensities and thresholds of conventional low-frequency SCS.


Pulsed ultrahigh-frequency spinal cord stimulation inhibited neuropathic pain–related behavior and paw stimulation evoked brain activation through mechanisms distinct from low-frequency SCS.

Editor’s Perspective
What We Already Know about This Topic
  • Spinal cord stimulation and application of pulsed radiofrequency to peripheral nerves are both well established pain treatment modalities
  • The question of how pulsed radiofrequency stimulation of the spinal cord affects pain is incompletely explored
What This Article Tells Us That Is New
  • In a rat model of neuropathic pain–related behavior, pulsed ultrahigh-frequency spinal cord stimulation induced a prolonged decrease in both mechanical and cold hypersensitivity
  • The effects of pulsed ultrahigh-frequency spinal cord stimulation on neuropathic pain–related behavior were associated with a reduction of evoked local field potentials in the somatosensory and anterior cingulate cortices