A randomised controlled trial (RCT) of peripheral nerve stimulation (PNS) at 10kHz frequency demonstrates a significant reduction in pain scores for patients suffering from chronic pain. While the authors—Philip Finch and colleagues from Perth Pain Management Centre (Perth, Australia)—reported that the decrease in pain and disability after stimulator implantation were maintained in both groups at three to six months, they found that these decreases were greater in PNS implants as opposed to spinal cord stimulator implants. These data were recently published in the journal Neuromodulation.
Regarding the current study, Finch and colleagues carried out an initial one-year clinical audit of patients undergoing permanent implantation of 10kHz frequency stimulators, for both spinal cord stimulation (SCS) for low back and lower limb pain, and for PNS for peripherally located chronic neuropathic pain. Following the positive results of this audit, the authors set out to design a double-blind RCT inclusive of PNS patients of whom were already implanted with 10kHz devices (Nevro)—with the device switched either ON or OFF in a randomised fashion. The double-blind approach was possible because 10kHz stimulation cannot be felt.
Through both the clinical audit and the subsequent RCT, Finch and his colleagues aimed to determine the effect of high-frequency stimulation on pain treated with a PNS system, including the time to commencement of analgesia once the device was switched ON, as well as time for pain to return once the device was switched OFF. Additionally, in the PNS group, sensory perception was examined for evidence of a sensory nerve conduction block appearing during stimulation.
The clinical audit assessed pain, disability and medication status for 12 months after stimulator implantation in 58 SCS patients (mean age: 55.8±13.4, 59% male), and in 11 PNS patients (mean age: 59.4±17.1 years, 46% female), between January 2013 and February 2017. Specifically, the PNS population was comprised of patients with an electrode positioned either along a branch of the occipital or trigeminal nerve (four), a limb nerve trunk (four), the S1 nerve root (one), the genito-femoral nerve (one) or the ileo-inguinal (one patient).
In this PNS cohort, a double-blind design was implemented to assess pain and other sensory modalities, before and after the stimulator was switched either ON or OFF for either two hours (protocol one) or four hours (protocol two).
The study investigators reported that decreases in pain and disability after stimulator implantation were maintained in both groups across the 12-month follow-up period. These decreases, however, were significantly greater in patients implanted with a PNS than SCS device (p=0.040). More precisely, in the PNS trial patients, pain increased after the system had been turned OFF overnight for at least 12 hours before testing. Furthermore, pain did not change following two hours of PNS, yet decreased significantly after four hours.
The authors also noted that analgesic use remained unchanged after spinal stimulator implantation, but significantly decreased for those implanted with the PNS device. Additionally, patients with a PNS implant reported higher satisfaction and less physical disability, compared to the SCS cohort. That being said, complication rates were similar for SCS and PNS implants (21 of 58 patients [36.2%], and 5 of 11 [45.5%], respectively). Similar problems were encountered regardless of the implant, including: wound infection, haematoma, lead migration, and a need to reposition the implantable pulse generator. Lastly, other sensory modalities were found to have been minimally affected by stimulation, regardless of its duration.
On discussion of the aforementioned findings, Finch and colleagues write: “The clinical audit confirmed the utility of treating both pain of spinal origin and peripheral sources with 10kHz stimulation.” Taking into account the fact that pain reduction was greater in the PNS group, they suggested that “this reflects the more specific single nerve anatomical targets for neuromodulation”, yet alternatively “might indicate differing mechanisms of peripheral neuromodulation to spinal stimulation”.
The study investigators acknowledged certain limitations to their study; primarily the small sample size and the uneven distribution between cohorts. Further, Finch and colleagues reported difficulty comparing the effect of SCS on pain of peripheral origin, with pain of peripheral origin treated with PNS, as the numbers were too low for statistical analysis. This being so, they stressed the need for this shortcoming to be addressed in future studies.
Finch and colleagues concluded that this is the first RCT that demonstrates a significant clinical effect on pain reduction using high frequency (10kHz) peripheral neuromodulation; specifically, a significant reduction in pain scores when stimulation was conducted for at least four hours. In addition, the authors maintained that the effects on peripheral sensory modalities were minimal—indicating that conduction block may not be an important mechanism in achieving adequate analgesia. This study was conducted without industry or outside funding support.