Conventional and Kilohertz-frequency Spinal Cord Stimulation Produces Intensity- and Frequency-dependent Inhibition of Mechanical Hypersensitivity in a Rat Model of Neuropathic Pain

Abstract

Background Spinal cord stimulation (SCS) is a useful neuromodulatory technique for treatment of certain neuropathic pain conditions. However, the optimal stimulation parameters remain unclear. Methods In rats after L5 spinal nerve ligation, we compared the inhibitory effects on mechanical hypersensitivity from bipolar SCS of different intensities (20%, 40%, 80% motor threshold) and frequencies (50-Hz, 1-kHz, and 10-kHz). We then compared the effects of 1-kHz and 50-Hz dorsal column stimulation at high and low stimulus intensities on conduction properties of afferent Aα/β-fibers and spinal wide-dynamic-range neuronal excitability. Results Three consecutive daily SCS at different frequencies progressively inhibited mechanical hypersensitivity in an intensity-dependent manner. At 80% motor threshold, the ipsilateral paw withdrawal threshold (%preinjury) increased significantly from pre-SCS measures, beginning with the first day of SCS at the frequencies of 1-kHz (50.2 ± 5.7% from 23.9 ± 2.6%, n = 19, mean ± SEM) and 10-kHz (50.8 ± 4.4 % from 27.9 ± 2.3%, n = 17), while it was significantly increased beginning on the second day in the 50-Hz group (38.9 ± 4.6% from 23.8 ± 2.1%, n = 17). At high intensity, both 1-kHz and 50-Hz dorsal column stimulation reduced Aα/β-compound action potential size recorded at the sciatic nerve, but only 1-kHz stimulation was partially effective at the lower intensity. The number of actions potentials in C-fiber component of wide-dynamic-range neuronal response to windup-inducing stimulation was significantly decreased after 50-Hz (147.4 ± 23.6 from 228.1 ± 39.0, n = 13), but not 1-kHz (n = 15), dorsal column stimulation. Conclusions Kilohertz SCS attenuated mechanical hypersensitivity in a time course and amplitude that differed from conventional 50-Hz SCS, and may involve different peripheral and spinal segmental mechanisms.

Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial

“…Others have shown that 1 kHz can be effective 16, 17, 18, 19. These results are consistent with preclinical studies showing that 1 and 10 kHz are approximately equally effective in reducing the mechanical hypersensitivity associated with neuropathic pain 20, 21, and that frequencies from 2 to 100 kHz all suppressed wide dynamic range (WDR) neuronal activity 22.…”

The Effect of High-Frequency Stimulation on Sensory Thresholds in Chronic Pain Patients

“…Research by Shechter et al [5] suggests that HFS reduces large Aα and Aβ fiber activity to a greater extent than does traditional SCS at 50 kHz. They also found that traditional SCS affected C-fiber activity to a greater extent than did HFS [5] . Furthermore, kilohertz-level SCS induced pain inhibition at lower amplitudes of stimulation with earlier onsets.…”

Spinal Stimulation for Pain: Future Applications

“…In a rat sciatic nerve ligation model both frequencies (1 kHz and 10 kHz) were effective, but the higher frequency was more effective in terms of onset of effect and its magnitude [9]. Clinical experience, however, showed that 5-kHz stimulation did not result in desired effects [13], whereas 10-kHz stimulation does relieve pain, but only at a very specific position of electrode contacts [11,12].…”

“…One suggestion, for example, was to replace conventional synchronous stimulation with a stochastic pattern in the hope that such irregular stimuli will be more effective in suppressing signal transmission in the central nervous system and perhaps prevent development of tolerance to stimulation [9]. It appears that the use of stochastic stimulation pattern so far has not been tested in laboratory or clinical settings.…”

“…The next steps in 10-kHz SCS will be to obtain regulatory approval in the USA based on an ongoing noninferiority study (NCT01609972) [14] and then test it in a variety of clinical conditions, perhaps defining those indications and those specific patient characteristics that are either unresponsive to conventional, lower-frequency SCS, or where a partial response makes more complete pain relief desirable. Recent experimental finding of hyperalgesia suppression [9] may translate into use of high-frequency SCS in allodynia and other neuropathic pain conditions. An expected step in high-frequency SCS technological development will be the creation of longer-lasting batteries, as current devices require daily or even twice-daily recharging owing to the high consumption of power.…”