Ramping up electrical frequency appears to alter neuronal activity in novel ways
by Stephani Sutherland on 14 Aug 2013
Spinal cord stimulation (SCS)—the delivery of pulses of electric current directly to the spinal cord via implanted electrodes—is an increasingly utilized pain treatment that gives some relief to about half of people with some types of neuropathic pain. Could it do better? This question has recently prompted researchers and clinicians to consider variations on the conventional SCS technique.
SCS typically involves electrical pulses delivered at a frequency of 50 hertz (Hz). Now, a study of SCS in animals suggests that high-frequency stimulation (at 1,000 or 10,000 Hz) can rapidly and effectively block pain hypersensitivity in a rat model of neuropathic pain and does so through a mechanism distinct from lower-frequency SCS. The findings provide insight into the physiological effects of SCS and suggest that alterations of the standard protocol may expand the potential use of SCS as a pain treatment. The results, from Yun Guan at Johns Hopkins University in Baltimore, Maryland, US, appeared in the August issue of Anesthesiology.
While several groups have recently investigated the clinical benefits of high-frequency SCS, the results have been mixed (Van Buyten et al., 2012; Tiede et al., 2013; Perruchoud et al., 2013). J. David Clark, an anesthesiologist at Stanford University in Palo Alto, California, US, wrote in an editorial accompanying the new paper that there has been “a conspicuous lack of … a clear physiological rationale for this approach” of using high-frequency stimulation. The new work addresses that need, he told PRF. Clark, who was not involved in the work, said the findings could lead to a better understanding of SCS that would allow practitioners to select among alternatives within the basic realm of electrical stimulation, although more work will be required to translate these findings in rodents to the clinic.
The research team, including first author Ronen Shechter, used a spinal nerve ligation model of neuropathic pain to investigate the analgesic and electrophysiological effects of SCS in rats. In behavioral experiments, the authors saw rats’ withdrawal threshold to mechanical stimuli fall after nerve damage—indicating hypersensitivity—and then recover with daily SCS treatment over three days. High-frequency (1 or 10 kHz) stimulation increased withdrawal threshold further and faster than conventional 50 Hz stimulation did, working on the first day of stimulation. The ultra-high frequency 10 kHz provided no added benefit beyond 1 kHz.
Next, the team tested the possibility that SCS at various frequencies might fundamentally alter the nerve fibers’ conduction properties. The researchers recorded from the peripheral sciatic nerve while evoking action potentials at the spinal cord in rats before and after high-frequency stimulation of the dorsal column, similar to therapeutic SCS. They found that mechanically sensitive Aα/β-fiber neurons were less active, particularly after high-frequency stimulation, suggesting these neurons had indeed toned down their excitability.
In another experiment, the researchers elicited wind-up in wide dynamic range (WDR) neurons in the dorsal horn, an experimental protocol thought to emulate spinal neuron hyperactivity in neuropathic pain. After conventional 50 Hz SCS, but not high-frequency 1 kHz SCS, pain-sensing C-fibers contributed less to WDR neuron activity, suggesting that less pain signal was getting through the spinal cord relay station en route to the brain. These findings indicated that several independent mechanisms may contribute to SCS-induced analgesia.
Just how SCS works to diminish pain remains enigmatic, but hypotheses to date have invoked the gate control theory, first described by Melzack and Wall in 1965. Still, “it’s not clear cut how that might work,” said Guan of the established framework. The theory holds that the experience of pain arises from the net total of sensory input from various modalities that goes through the “gate” of second-order spinal cord neurons. If nociceptive C-fibers dominate the input, the result is pain; if input from mechanically sensitive A-fibers can be amplified, pain is reduced. One of Guan’s experiments supports this theory: Conventional SCS decreased C-fiber input to WDR neurons. The other finding, that A-fibers’ conduction was affected by high-frequency stimulation, suggests another road to analgesia. And yet another distinct mechanism probably contributes to SCS analgesia: activation of higher brain areas that control descending pain modulation (Linderoth and Meyerson, 2010).
The variable response to conventional SCS among patients with pain may stem from the fact that different types of pain arise from different nerve activities. About one fifth of people with neuropathic pain experience mechanical hypersensitivity, or allodynia—a painful sensation to a normally non-noxious touch—which is modeled in the rodent nerve injury used in the current study. Allodynia is thought to arise from A-fiber activity and so might be better treated with the high-frequency SCS that slowed A-fiber conduction. On the other hand, the results suggest that different types of pain involving overactive input from C-fibers might respond better to conventional SCS.
Guan added that their findings “indicate that the two frequencies may have different uses or applications. When patients don’t respond to one frequency, maybe they should try another.”
Although much work remains to understand and optimize SCS, Guan said, the work adds flexibility to the technique. Treating neuropathic pain is “like fighting a battle,” he said, and better weapons are always welcome.
Stephani Sutherland, PhD, is a neuroscientist, yogi, and freelance writer in Southern California.
http://www.painresearchforum.org/news/30637-spinal-cord-stimulation-promising-variation-theme
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