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

Abstract

ObjectiveThe PROCO RCT is a multicenter, double‐blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate on analgesia in kilohertz frequency (1–10 kHz) spinal cord stimulation (SCS).Materials and MethodsPatients were implanted with SCS systems and underwent an eight‐week search to identify the best location (“sweet spot”) of stimulation at 10 kHz within the searched region (T8–T11). An electronic diary (e‐diary) prompted patients for pain scores three times per day. Patients who responded to 10 kHz per e‐diary numeric rating scale (ED‐NRS) pain scores proceeded to double‐blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy.ResultsAll frequencies provided equivalent pain relief as measured by ED‐NRS (p ≤ 0.002). However, mean charge per second differed across frequencies, with 1 kHz SCS requiring 60–70% less charge than higher frequencies (p ≤ 0.0002).ConclusionsThe PROCO RCT provides Level I evidence for equivalent pain relief from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz required significantly less charge than higher frequencies.

Temperature increases by kilohertz frequency spinal cord stimulation

“…In the context of kHz-SCS, this study specifically addressed joule heat with the hypothesis that by increased power (pulse compression), kHz-SCS waveforms will superlinearly increase tissue temperature, potentially inducing downstream alterations in tissue function with therapeutic effects in chronic pain. Characteristic clinical responses to kHZ-SCS including as the lack of associated neural sequelae such as paresthesia and the frequency insensitivity of efficacy 52 reconcile well with joule heating, while the delayed time course of effects 53 may be explain by temperature homeostatic responses or heat shock protein regulation of neuroinflammation.…”

“…heat shock proteins). Slow temperature homeostatic changes provide a plausible explanation for the delayed onset of pain relief by kHz-SCS 52,53 and suggest specific molecular pathways (MoA) for pain relief including heat shock protein producing downregulation of neuroinflammation. For example, 72-kDa heat shock protein (Hsp70) inhibits activation of the pro-neuroinflammatory transcription factor, nuclear factor-kB in satellite glial cells (NF-kB) 66 .…”

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation

“…Why this location is critical is unknown, and it was questioned in a recent clinical study that explored locations within the T8–T11 range using SCS at 10 kHz (Thomson et al. ).…”

“…Considering that stimulation over a particular spinal segment is entirely empirical and that no clear mechanism has been proposed to explain the clinically observed effects of high‐frequency SCS, Thomson et al. () searched for the optimal stimulation location (‘sweet spot’) within the T8–T11 vertebral segments. Electrical bipoles were activated at 10 kHz, with a pulse width of 30 μs, and current amplitude titrated to optimize therapy.…”

Long-Term Effect of Peripheral Nerve Field Stimulation as Add-On Therapy to Spinal Cord Stimulation to Treat Low Back Pain in Failed Back Surgery Syndrome Patients: A 12-Month Follow-Up of a Randomized Controlled Study

“…In the PROCO RCT by Thomson et al found in 20 patients, implanted with SCS systems, equal pain relief at 1 and 10 kHz. At 1 kHz significant less charge was needed compared to 10 kHz .…”