Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain

Abstract

Chronic pain remains a leading cause of disability worldwide, and there is still a clinical reliance on opioids despite the medical side effects associated with their use and societal impacts associated with their abuse. An alternative approach is the use of electrical neuromodulation to produce analgesia. Direct current can block action potential propagation but leads to tissue damage if maintained. We have developed a form of ultra low frequency (ULF) biphasic current and studied its effects. In anesthetized rats, this waveform produced a rapidly developing and completely reversible conduction block in >85% of spinal sensory nerve fibers excited by peripheral stimulation. Sustained ULF currents at lower amplitudes led to a slower onset but reversible conduction block. Similar changes were seen in an animal model of neuropathic pain, where ULF waveforms blocked sensory neuron ectopic activity, known to be an important driver of clinical neuropathic pain. Using a computational model, we showed that prolonged ULF currents could induce accumulation of extracellular potassium, accounting for the slowly developing block observed in rats. Last, we tested the analgesic effects of epidural ULF currents in 20 subjects with chronic leg and back pain. Pain ratings improved by 90% after 2 weeks. One week after explanting the electrodes, pain ratings reverted to 72% of pretreatment screening value. We conclude that epidural spinal ULF neuromodulation represents a promising therapy for treating chronic pain.

Spinal cord stimulation restores sensation, improves function, and reduces phantom pain after transtibial amputation

“…Subject 3 also reported that PLP increased when testing was paused for a week. The recurrence of PLP aligns with anecdotal evidence from traditional SCS studies which report that the wash-in and wash-out period of SCS can be 3-7 days 35 . Our observations build on growing evidence that somatosensory neuroprosthetic systems are associated with a decrease in PLP 7,[11][12][13][14] .…”

White matter tract transcranial ultrasound stimulation, a computational study

“…This could potentially cause a greater change in the BOLD signal activity being measured in the ROIs after TUS, which causes a greater loss of activity coupling between the ACC and these regions. Such observation feeds directly into the wider discussion of the use of neuromodulation for pain management, where a current is understood to block the signal in a similar fashion [72,73].…”

The Effect of Pre-Electroacupuncture on Nociceptive Discharges of Spinal Wide Dynamic Range Neurons in Rat

“…Behavior and electrophysiological evidence have demonstrated that activation of low-threshold mechanoreceptors could alleviate pain symptoms and inhibit the spontaneous discharges of dorsal horn neurons. [39][40][41][42] This analgesic effect has been generally explained by the gate control theory, which suggests that the nociceptive (Aδ/C) inputs are gated by feed-forward activation of non-nociceptive (Aβ) afferents in SDH. The spinal WDR neurons receive inputs from both non-nociceptive (Aβ) and noxious (Aδ and C) afferents.…”