Clinical study of a micro-implantable pulse generator for the treatment of peripheral neuropathic pain: 3-month and 6-month results from the COMFORT-randomised controlled trial.

BACKGROUND: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG). METHODS: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle. RESULTS: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable. CONCLUSIONS: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

Design of a Multicenter, Randomized Controlled Trial for the Treatment of Peripheral Neuropathic Pain (COMFORT Study) with a Micro-Implantable Pulse Generator.

Background: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.

Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm³ in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (<1.5 cm³ in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months.

Combination therapy with simultaneous delivery of spinal cord stimulation modalities: COMBO randomized controlled trial.

Aim: The Combining Mechanisms for Better Outcomes randomized controlled trial assessed the effectiveness of various spinal cord stimulation (SCS) modalities for chronic pain. Specifically, combination therapy (simultaneous use of customized sub-perception field and paresthesia-based SCS) versus monotherapy (paresthesia-based SCS) was evaluated. Methods: Participants were prospectively enrolled (key inclusion criterion: chronic pain for ≥6 months). Primary end point was the proportion with ≥50% pain reduction without increased opioids at the 3 month follow-up. Patients were followed for 2 years. Results: The primary end point was met (n = 89; p < 0.0001) in 88% of patients in the combination-therapy arm (n = 36/41) and 71% in the monotherapy arm (n = 34/48). Responder rates at 1 and 2 years (with available SCS modalities) were 84% and 85%, respectively. Sustained functional outcomes improvement was observed out to 2 years. Conclusion: SCS-based combination therapy can improve outcomes in patients with chronic pain. Clinical Trial Registration: NCT03689920 (ClinicalTrials.gov), Combining Mechanisms for Better Outcomes (COMBO).

Spinal cord stimulation (SCS) is a device-based therapy for chronic pain that delivers electrical impulses to the spinal cord, disrupting pain signals to the brain. Pain relief can be achieved using different SCS techniques that use or do not use paresthesia (stimulation that produces a tingling sensation). These approaches affect patients in different ways, suggesting that different biological processes are involved in enabling pain relief. Research also suggests that better long-term results occur when patients can choose the therapy that is best for their own needs. This clinical study compared pain relief and other functional activities in those receiving combination therapy (simultaneous use of SCS that does and does not produce tingling sensation) against those receiving monotherapy (only SCS therapy producing tingling sensation) for 3 months. In the study, 88% of those receiving combination therapy and 71% with monotherapy alone reported a 50% (or greater) decrease in overall pain (the 'responder rate') without an increased dose of opioid drugs at 3 months after the start of therapy. This responder rate was found to be 84% at 1 year and 85% at 2 years (with all SCS therapy options available). Analysis of functional activities or disability showed that patients improved from 'severely disabled' at study start to 'moderately disabled' after 2 years, indicating that effective long-term (2 year) improvement can be achieved using SCS-based combination therapy for chronic pain.

Landmark-based versus ultrasound-guided ilioinguinal/iliohypogastric nerve blocks in the treatment of chronic postherniorrhaphy groin pain: a retrospective study.

BACKGROUND: Chronic postherniorrhaphy groin pain (CPGP) is a debilitating condition, which is often refractory to conservative medical management. To our knowledge, there have been no studies directly comparing landmarked-based and ultrasound-guided approaches in this population. OBJECTIVE: To compare the effectiveness of landmark-based and ultrasound-guided ilioinguinal/iliohypogastric nerve blocks in the treatment of CPGP. STUDY DESIGN: This is a retrospective chart review of patients who presented to our tertiary care pain medicine clinic with a diagnosis of CPGP. Inclusion criteria were the following: age >18 years, diagnosis of groin pain, and prior history of herniorrhaphy. Exclusion criteria included those who were seen for initial consultation but were lost to follow-up. Primary outcomes were 50% or greater reduction in pain on visual analog scale (VAS). Secondary outcomes were 30% or greater reduction in VAS pain score, changes in VAS pain scores, and reported complications. RESULTS: A total of 36 patients were included in the study. Of them, 20 patients underwent the landmark-based and 16 underwent the ultrasound-guided techniques. There was no significant difference in baseline demographics. The average VAS score preinjection was 7.08 in the landmark-based and 7.0 in the ultrasound-guided groups (P=0.65). A total of 14 patients (70%) in the landmark-based and eleven patients (79%) in the ultrasound-guided groups experienced at least a 50% reduction in VAS scores. There was no statistically significant difference between the two groups (P=1.0), and no complications were noted. We also did not find a significant difference in terms of number of patients with 30% or greater reduction (P=0.71) and changes in VAS pain scores (P=0.64). No complications were reported in either group. CONCLUSION: In our study, there was no statistically significant difference between the landmark-based and ultrasound-guided groups in terms of a reduction in VAS pain scores, and no complications were noted in either group.

Interventional modalities to treat cancer-related pain.

Cancer-related pain is a significant cause of morbidity in those affected by both primary and metastatic disease. Although oral, transdermal, and parenteral opioid medications are an integral part of the World Health Organization's analgesic ladder, their use may be limited by side effects. Fortunately, there are advanced interventional pain management strategies effective in reducing pain in the cancer patient while mitigating the aforementioned side effects. Celiac plexus blocks and neurolysis have been proven effective in treating cancers of the abdominal viscera (ie, pancreas). Transversus abdominis plane blocks, neurolysis, and catheter placement can be used to treat cancer pain associated with the abdominal wall. Peripheral nerve blocks and catheter placement at the brachial and lumbosacral plexus or peripheral nerves treat cancer pain associated with the upper and lower limbs, whereas paravertebral and intercostal blocks treat cancer pain associated with the chest wall and ribs. Finally, alternate drug delivery methods such as intrathecal drug delivery systems concentrate medication at central opioid receptors without affecting the peripheral receptors implicated in unwanted side effects. This article provides an overview of these interventions, including indications, contraindications, and potential complications of advanced interventional pain management options available for the treatment of intractable cancer-related pain.

Management of Dupuytren contracture with ultrasound-guided lidocaine injection and needle aponeurotomy coupled with osteopathic manipulative treatment.

Dupuytren contracture is a debilitating disease that characteristically presents as a firm nodularity on the palmar surface of the hand with coalescing cords of soft tissue on the webs and digits. With few nonsurgical modalities providing clinical benefits, open surgical procedures are the standard of care for patients with this condition. However, recent studies have associated surgical intervention with many complications, necessitating further exploration of nonsurgical treatment options. We describe the case of a 64-year-old woman who presented with decreased extension of the fourth and fifth digits on the upper extremities bilaterally; previous conservative treatment regimens had been unsuccessful. After a diagnostic ultrasound, the patient was diagnosed as having Dupuytren contracture and underwent 5 treatments consisting of ultrasound-guided dry-needle aponeurotomy, lidocaine injections, and osteopathic manipulative treatment. During the fifth treatment session, the patient experienced dramatic relief of her symptoms after a palpable release during the manual manipulation portion of her therapeutic regimen. At 2-week follow-up, the patient was symptom-free. Based on this desirable outcome, the authors suggest future research be directed at minimally invasive therapeutic options in the management of Dupuytren contracture.