1. 2025;28;417-429A Prospective, Randomized, Controlled Clinical Trial of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator for the Treatment of Chronic Craniofacial Pain
   Randomized Controlled Trial
   Salim M. Hayek, MD, PhD, Nameer Haider, MD, Ashwin Viswanathan, MD, Mehul Desai, MD, Jeffrey Rosenberg, MD, and Niek E. Vanquathem, BS.

BACKGROUND: Craniofacial pain is one of the most common chronic pain conditions, affecting more than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

OBJECTIVE: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain. 

STUDY DESIGN: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

SETTING: This study was conducted in 7 clinical sites in the US.

METHODS: All patients in this randomized controlled trial (RCT) were permanently implanted with the Freedom® Peripheral Nerve Stimulator (PNS) System (Curonix LLC). All patients completed an initial 7-day therapy assessment period following the permanent implantation. The patients who successfully completed the initial 7-day therapy assessment period (>= 50% pain relief) were randomly assigned to either a patient group that received continued stimulation (the “active” arm) or a patient group whose treatment was discontinued for 3 months after the initial positive 7-day therapy assessment period (the “deactivated” stimulation arm). After the 3-month follow-up visit, the deactivated patients were reactivated. The primary efficacy outcome included the proportion of patients who experienced significant pain relief (>= 50%) 3 months after the permanent implant procedure. The visual analog scale (VAS), Brief Pain Inventory Facial (BPIF) questionnaire, and Short-Form McGill Pain Questionnaire 2 (MPQ-SF-2) were used to measure changes in pain. Additional functional outcome measures included the Patient Global Impression of Change (PGIC) and the 36-Item Short-Form Survey (SF-36).

RESULTS: During the 7-day therapy assessment period, 56 out of 60 patients reported significant pain relief (>= 50%), representing a 93% responder rate. At 3 months, 69% of the active stimulation group experienced significant pain relief, while only 11% of the deactivated group reported significant pain relief. The mean VAS scores were reduced by 62% and 8.5% in the active and deactivated stimulation groups. When patients within the deactivated group were reactivated after 3 months, the reactivated patients reported similar reduction in pain scores to those reported by the active arm patients. Similar results were found for the functional outcome measures. After the reactivation, significant pain relief was maintained through the 12-month follow-up period. No SAEs were reported throughout the study for any of the patients. 

LIMITATIONS: Limitations include the lack of true placebo due to the required use or nonuse of the external transmitter as control per the study design, the optional utilization of supra- or sub-threshold stimulation, and variations in patient follow-up due to the COVID-19 pandemic.

CONCLUSION: This RCT operated under an IDE requiring regulatory FDA oversight. This study provides Level 1 evidence for PNS therapy. The positive outcomes of this study support an expanded PNS indication for the treatment of craniofacial pain. The study confirms that HF-EMC powered permanent PNS is an effective and safe intervention for refractory chronic craniofacial neuropathic pain.

KEY WORDS: HF-EMC powered permanent peripheral nerve stimulator (PNS), peripheral nerve stimulation (PNS), peripheral nerve stimulation interventional techniques, peripheral neuropathic pain, chronic pain, chronic craniofacial pain, occipital nerve, trigeminal nerve, craniofacial peripheral nerve stimulation (CFPNS)