Lower frequencies of dorsal root ganglion stimulation (DRG-S) may be more effective in the treatment of neuropathic pain—as per a late-breaking presentation from Guilherme Santos Piedade (University of Düsseldorf, Düsseldorf, Germany) at this year’s North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA).
Piedade relayed the results of a randomised clinical trial in which several levels of DRG-S frequency, from 20Hz to 80Hz, were assessed in patients with various pain aetiologies. A number of measures including pain intensity, quality of life and depression were used by the investigators to evaluate the effectiveness of DRG-S therapy.
“In this study, lower stimulation frequency—as low as 20Hz—was able to treat patients with neuropathic pain more effectively,” Piedade told the NANS 2022 audience. “And, we are already doing [further] studies to record and document the effect of even lower stimulation frequencies. We think that it is very important to consider battery lifetime, but we are also excited by the idea that we can target different neurocomponents of the DRG with different stimulation frequencies.
Piedade began with a nod to previously published studies in this space, which have alluded to the effect DRG-S frequency can have on therapy outcomes. As such, he and his colleagues conducted what is—to the best of their knowledge—the first randomised, double-blinded trial to directly assess this link regarding DRG-S.
They enrolled a total of 19 patients (mean age=53 years) who had already been receiving DRG-S for a mean total of 17.2 months. Seven of these patients were receiving DRG-S therapy for complex regional pain syndrome (CRPS). Other notable pain aetiologies included postsurgical pain after arthroplasty (n=4) and postherpetic neuralgia (n=3), Piedade reported.
Frequencies of 20Hz, 40Hz, 60Hz and 80Hz, as well as a sham stimulation protocol, were tested in the study, with stimulation lasting for four days prior to a two-day washout period. Each patient was followed for a total of five weeks, using the visual analogue scale (VAS) for pain intensity, the McGill pain questionnaire, quality of life measures, and the Beck depression inventory, to assess DRG-S outcomes.
Prior to disclosing results from the study, Piedade also noted a couple of “very important” points, with the first being the fact that DRG-S was amplitude corrected for each of the tested frequencies, so that every patient was stimulated at a subthreshold level each week. Secondly, he detailed that every patient was undergoing DRG-S at a standard frequency of 20Hz before the study was initiated.
Piedade reported a baseline VAS score of 3.9—which was similar to the mean score of 3.7 achieved with 20Hz in the study itself. He went on to note a statistically increase in patient VAS scores at 40Hz, to 4.9. “And, when you increase the frequency even more, to 60Hz and 80Hz, you see that patients get worse and achieve pain intensity scores of 5.8,” he added. Piedade also said that a pain intensity score of 8.6 was seen with sham stimulation, and this was close to the pre-implantation VAS scores observed within the retrospective patient data.
“It is very curious to see that, for patients with a painDETECT questionnaire [PD-Q] score lower than 12—meaning that they have a strong nociceptive component—the frequency had no real effect over stimulation on pain intensity scores,” he continued. “Unfortunately, we only have five patients in this situation, so we could not achieve statistical significance here, but it is still a very interesting find.”
In addition to the statistically significant difference in pain intensity scores between 20Hz and 40Hz, Piedade claimed that the same trend was seen in every other outcome measure used in the study. “Higher frequencies led to worse quality of life, and worse scores on McGill pain questionnaire and Beck depression inventory,” he stated. “We must say that this effect was not always statistically significant—as seen in pain intensity scores—but the trend is surely there.”
Speculating on the reasons behind these findings, Piedade referred to the phenomenon of ‘phase locking’, which has been outlined in previous studies and literature on DRG-S. Phase locking, he continued, is the ability of nerve tissue to fire neurons at the same frequency as that of the stimulation being administered—something that is only possible up to 20Hz. This phenomenon is caused by as-yet unexplained neurophysiological properties, according to Piedade.
Assessing the study itself in more depth, the speaker said that a washout period of two days was adequate for assessing pain control, but not for autonomic symptoms, and future studies involving CRPS could therefore benefit from longer washout periods. He added that the study was strengthened by the fact it included multiple pain aetiologies—creating an inhomogeneous group—but it was “underpowered” to show a statistically significant difference between PD-Q scores above and below 12.
Piedade concluded by noting that it would also be “very interesting” to see if there are differences in the effect of stimulation frequency over different pain aetiologies like CRPS, and stated that larger studies in this space would be valuable moving forward.
The results of Piedade and his colleagues’ study have now been published online in the journal Functional Neurosurgery—Pain. In their report, the researchers conclude that “the choice of the [DRG] stimulation frequency shows a clear influence on pain reduction and quality of life”, before adding: “Lower stimulation frequencies seem to be most effective in neuropathic pain.”
