The study, of 20 patients with stubborn low back pain, tested the effects of implanting electrodes near the spinal cord to stimulate it with “ultra-low” frequency electrical pulses.
After two weeks, 90% of the patients were reporting at least an 80% reduction in their pain ratings, the researchers found.
“That improvement is almost too good to be true,” said Dr. Houman Danesh, who directs the division of integrative pain management at Mount Sinai Hospital in New York City.
Danesh, who was not involved in the study, said the results could be skewed because the patient group was so small. On the other hand, he said, it’s possible the researchers “have really caught onto something.”
Only larger, longer-term studies can answer that question, Danesh said.
It’s not that electrical stimulation, per se, is unproven for back pain: Pain management specialists, including Danesh, already offer the approach to some patients.
It can be done non-invasively, through transcutaneous electrical nerve stimulation (TENS) – where electrodes are placed on the skin over areas of pain, to deliver electrical pulses to the underlying nerves.
Another option is spinal cord stimulation. There, doctors implant electrodes near the spinal cord, along with a pulse generator that is placed under the skin of the buttocks or abdomen. Patients can then use a remote control to send electrical pulses to the spinal cord when they are in pain.
The theory is that the stimulation interrupts the spinal cord’s transmission of pain signals to the brain.
Right now, spinal cord stimulation is reserved for certain tough cases of back pain – for example, when people continue to have pain even after back surgery, Danesh said.
The effectiveness of the approach, though, varies from person to person, and researchers have been looking at ways to refine it.
For the new study, a U.K./U.S. team tested what it’s calling ultra-low frequency spinal cord stimulation.
The researchers started with lab experiments in rats, finding that the electrical pulses blocked most transmissions of pain signals along the spinal cord – in a manner that seems distinct from current spinal cord stimulation techniques.
They then moved on to 20 patients with chronic low back pain, many of whom also had pain running down the leg (commonly known as sciatica). The researchers implanted electrodes in all 20; two patients dropped out due to infection at the surgical site.
Among the 18 patients who finished the two-week study, pain ratings improved by an average of 90%. Nearly all of the patients had improvements of at least 80%.
When the electrodes were removed, patients’ back pain came roaring back, according to findings published Aug. 25 in the journal Science Translational Medicine.
“The pain improvement is dramatic—that’s one of the features of this treatment that we find so impressive,” said senior researcher Stephen McMahon, who directs the London Pain Consortium at King’s College London in the United Kingdom.
“Other successful pain therapies more typically find 30% to 50% clinical improvement,” he added.
One of the strengths of this early study is that it “shows directly a powerful inhibition of pain-related signals,” McMahon noted.
Having identified “such a robust mechanism,” he added, it may be possible to use the technique for a range of conditions other than back pain.
The study was funded by Presidio Medical, Inc., of South San Francisco, which is developing the technology.
Danesh said, “I think this is continuing a trend of a technological jump in the use of spinal cord stimulation.”
However, he stressed, no matter what treatments people use for low back pain, some low-tech fundamentals remain key—namely, addressing bad posture habits and muscle strength imbalances.
Sitting all day, and the resulting weakening of the gluteal muscles (in the buttocks), is a big culprit, Danesh noted.
So strengthening those muscles, along with being generally active, is a must.
“You have to be mobile, when you’re in pain and when you’re not,” Danesh said. “Movement is medicine.”
The field of spinal cord stimulation (SCS) owes its inception to the concept of gate control theory (GCT), put forth by Wall and Melzack in their landmark 1965 paper, which proposed that “control of pain may be achieved by selectively activating the large, rapidly conducting fibers”.1 The first reported clinical application of dorsal column stimulation came 2 years later, and the field has gradually expanded ever since.
Today, an estimated 50,000 spinal cord neurostimulators are implanted annually.4, 5 The growth of neurostimulation has been fueled in part by the increasing prevalence of neuropathic pain,6 in particular the upsurge of patients with failed back surgery syndrome (FBSS),7,8 and the attempts to use strategies other than chronic opioid therapy to treat chronic neuropathic pain.
Although SCS technology has developed greatly in the past decades,9 the last few years have witnessed the introduction of several novel devices and stimulation modalities, including high- frequency technology,10, 11 dorsal root ganglion (DRG) stimulation,12 burst stimulation,13 and other paradigms.14–16
Some of the new waveforms, such has high-frequency stimulation, have challenged our ability to elucidate their mechanisms of action within the framework of the GCT. Fundamentally, SCS, regardless of type, involves the generation of electric fields between metal contacts residing in the epidural space. The applied fields change the electrical potential across membranes based on the properties of tissues near the electrode, such as the dura, layer of cerebrospinal fluid, and white matter.
In the case of excitable membranes, such as those found in nearby dorsal column axons, the electric field can trigger one or more action potentials, depending on the bioelectrical properties of the axon (diameter, myelination status, and electrical threshold). As electrodes are typically placed near the physiological midline of the dorsal columns (except in the case of DRG stimulation), electrical stimulation causes activation of dorsal column axons, resulting in orthodromic and antidromic transmission of action potentials that generate segmental and supraspinal effects2, 14, 17–20 (Figure 1).
Large diameter axons have low thresholds for firing action potentials, and thus are preferrentially activated over smaller fibers. The bioelectrical properties of the spinal cord have received signficant attention, and a number of reviews have been published on this topic.14, 21, 22 Conventional SCS preferentially activates large Ap dorsal column axons.
This activation can be measured as action potentials propagated antidromically in peripheral nerves,23, 24 as epidural action potentials,25, 26 as somatosensory evoked potentials recorded on the scalp,25 and as muscle twitches in limb and trunk muscles,27, 28 and felt by patients as paresthesias.29 In addition to provoking action potentials, electrical stimulation alters the membrane potential of neurons and other cell types exposed to electric fields, thereby altering electrochemical properties of the segments affected.17, 30

Spinal cord stimulation lead position.
The electrical lead sits in the epidural space, and the electrical stimuli activate fibers directly below it. This causes initiation of orthodromic and antidromic action potentials and supraspinal and segmental effects. Adapted from Smits et al., 2013.2
Electrical charge can be delievered via various waveforms, and net effects depend on waveform characteristics. The waveforms generated can be characterized in relation to the pulse amplitude, width, and frequency, which combine to deliver a specific amount of charge to tissues. The amount of charge delievered is believed to be fundamental to the electrical fields generated and subsequent recruitment of nerves.14, 21, 31
As device electronics have improved, the ability to deliver electrical impulses precisely with specific waveforms and various cathode/anode combinations has grown exponentially. Conventional, burst, and high-frequency stimulation differ based on frequencies, waveform patterns, and how charge transfer is balanced (Figure 2), and thus produce different patterns of activation of axons and adjacent neural tissues.
Burst is unique in how charge balance is handled: the burst of five individual constant current pulses is charge balanced at the end of burst, instead of for each spike (Figure 2, panel B).13
Signficant debate exists regarding what fibers are activated by SCS, and how fiber activation varies for the different waveform patterns and intesities.21, 22, 32–34 Furthermore, it is unclear which specific fibers need to be activated to achieve optimal pain relief, and how activation patterns change in chronic SCS.

Waveform properties.
(A) The amount of charge delivered to tissues depends on pulse properties: shape, amplitude, and duration. The lower panel illustrates the concept of frequency and charge balance. (B) Burst waveform, adapted from De Ridder et al.3 The waveform represents five, 1-ms-long pulses, delivered at 500 Hz, while the burst frequency is 40 Hz. Charge balance occurs after the five pulses.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391880/
More information: Martyn G. Jones et al, Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abg9890