Chronic pain, classified as persistent pain that lasts longer than three to six months, remains an area of considerable unmet medical need. A new treatment that uses electrodes to deliver alternating pulses of ultralow-frequency (ULF) current could help address this need. In a pilot trial, the treatment improved pain ratings by as much as 90% after 15 days of use. Unlike existing clinical neuromodulation techniques, this ULF approach avoids tissue damage and other side effects.
The research team, headed up at Kings College London, used experimental, theoretical and clinical approaches to investigate the potential of the new ULF neuromodulation technique. In research described in Science Translational Medicine, the team examined whether ULF current waveforms can effectively impede the conduction of sensory signals in laboratory rats and reduce chronic pain in patients.
Neuromodulation, the use of electrical currents to block the transmission of pain signals between neurons, has been employed as a non-pharmacological treatment for chronic pain for decades. Existing technologies, however, can be invasive, have limited efficacy and cause side effects.
Spinal cord stimulation, for example, utilizes an implanted device to produce pulsed electrical signals in the region of the spinal cord. The treatment has had limited clinical success, only working for some patients and alleviating pain for short periods of time. It can also cause paresthesia, a sensation of numbness, tingling or burning. Previous research has also explored the application of direct current (DC), which can effectively block the conduction of action potentials (which transmit pain signals), but leads to tissue damage and electrode degradation if maintained.
In this latest work, Stephen McMahon from the Wolfson Centre for Age-Related Diseases and collaborators developed a form of ULF biphasic current. Because the slowly cycling current waveform has a period of more than 10 s, far longer than the millisecond time constant of neuronal action potentials, it effectively mimics DC conditions, but with alternating polarity that avoids potential tissue or electrode damage. Using computational modelling, they determined that the mechanism of immediate conduction block at the plateau phases of the ULF waveform was the same as that produced by DC.
In anesthetized rats, this waveform produced a rapidly developing and completely reversible conduction block in more than 85% of spinal sensory nerve fibres excited by peripheral stimulation. Sustained ULF currents at lower amplitudes led to a slower onset but reversible block. In separate experiments, the researchers verified that ULF currents blocked sensory neuron ectopic activity, an important driver of neuropathic pain, in rats with spinal nerve injury.
Clinical evaluation
The team tested the efficacy of epidural ULF therapy in 20 patients with chronic lower back pain. Eighteen patients received the full treatment during five clinical visits over 15 days, with two withdrawing early due to surgical site infections. The therapy was well tolerated, with none of the patients experiencing muscle weakness or paresthesia.
The researchers assessed pain using the visual analogue scale (VAS), in which patients report their pain level as a distance along a 100 mm line, ranging from no pain at 0 mm to severe pain at the far end. Epidural ULF significantly reduced the patients’ pain ratings, from a mean score of 74.6±1.6 mm at screening, to 15.7±4.1 mm at day seven, and 7.6±3.1 mm at day 15. These changes represent 79% and 90% reduction in pain ratings, respectively. One week after the treatment finished, pain had begun to increase again, ultimately reverting to original values.
Study participants reported that pain started to reduce within 2 to 12 hr of the initial treatment, and increased again within one day of ULF cessation. During the treatment time, the subjects found it easier to take walks and perform other types of physical activity. Seven of the 19 patients who received at least seven days of treatment achieved 100% back pain relief, with an additional 10 achieving at least an 80% improvement, and another achieving 50% pain relief.
Pulsed radiofrequency therapy relieves acute back pain
Eleven participants also suffered from leg pain, with a VAS score of 69.5±5.6 mm at screening. This score reduced to 5.1±2.0 mm on the final day of treatment. Six patients achieved 100% pain relief, an additional four achieved 80% or greater, and one achieved 50% pain relief.
The researchers conclude that ULF could provide an effective alternative treatment for chronic pain, noting that their results warrant longer studies to define the technique’s long-term safety and further interrogate its mechanisms of action.
