The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

A Review of the Factors and Outcomes of Institutional Interdisciplinary Neuromodulation Committees: A Multicenter Experience.

INTRODUCTION: Neuromodulation represents one of the more advanced tools in the armamentarium of pain physicians. To optimize neuromodulation patient selection and management, an institutional interdisciplinary neuromodulation committee was created at each of two academic medical centers (University of California Davis [UCD] and Stanford University). The committee aims to collaboratively optimize neuromodulation candidates, to assess and minimize medical and psychologic risks, and to select the best device given a patient's pain condition. In this study, we present the methods and outcome data of the Neuromodulation Committee at the two institutions. MATERIALS AND METHODS: After institutional review board approval, we included all adult patients who were evaluated by the Neuromodulation Committee between 2017 and 2020 at two academic pain clinics. Patients with insufficient data were excluded from the study. A retrospective chart review was completed on 385 UCD and Stanford University patient committee reviews. Data collected from the chart review included demographics (age, sex), committee meeting results (proceed with trial/implant or decline), trial success, and implant rate. RESULTS: Of the 385 patients screened, the committees recommended proceeding with an implantable device (peripheral and neuraxial) in 337 patients (87.5%). Of the 278 patients recommended for neuraxial neuromodulation, 131 underwent trials with percutaneous leads (47.1%). Trials were successful (causing a ≥50% reduction in self-reported pain or improved function) in 108 patients (82.4%). The institutions completed 87 implants of 131 trials, representing a trial-to-permanent ratio of 66.4%. CONCLUSIONS: The Neuromodulation Committee aims to identify optimal patients for neuromodulation, address procedural challenges, decrease adverse events, provide educational context for trainees, and improve patient-related outcomes. Patients who were recommended for neuromodulation and subsequently underwent intervention had high trial success rates for dorsal root ganglion stimulation and spinal cord stimulation. The findings indicate that such an approach can lead to neuromodulation success, especially at academic centers, by combining the expertise of both medical and psychologic professionals.

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Application of multidisciplinary team conference for neuromodulation candidates facilitates patient selection and optimization.

Introduction: Psychological evaluation is required by insurance companies in the United States prior to proceeding with a spinal cord stimulation or a dorsal root ganglion stimulation trial. Since January 2017, we implemented a Multidisciplinary Team Conference for Neuromodulation in our center to facilitate the collaboration between pain physicians and psychologists and to optimize screening of neuromodulation candidates. This study aims to report the impact of this team conference on improvement of neuromodulation outcome in our center. Methods: Appropriateness of neuromodulation were discussed in the team conference after initial visit with the pain specialist and psychological evaluation. For this study, we prospectively and retrospectively collected data on neuromodulation candidates who went through the team conference and those who did not as controls. Results: We discussed 461 patients in the team conference sessions from January 2017 to July 2023. Out of these, a spinal cord stimulator or a dorsal root ganglion stimulator trial was performed in 164 patients with 80.5% (132 cases) trial success rate leading to 140 implants. Out of these implants, 26 (18.6%) explanted and 21 (15%) required revision in 41 (29.3%) patients. We performed neuraxial neuromodulation trial for 70 patients without going through the team conference from January 2016 to July 2023 with a trial success rate of 45.7% (32 cases). In this group, 7 (21.9%) and 6 (18.8%) patients underwent explant and revision. The differences between the groups were statistically significant for trial success rate (odds ratio of 4.9 with p-value of <0.01) but not for explant (odds ratio of 0.8 with p-value of 0.627) or revision (odds ratio of 0.8 with p-value of 0.595). Conclusion: Implementing Multidisciplinary Team Conference increased trial success rate in our center. Team conference provides therapeutic benefit for patients, and also provides the opportunity for an educational discussion for trainees.

Considerations in permanent implantation of peripheral nerve stimulation (PNS) for chronic neuropathic pain: An international cross-sectional survey of implanters.

AIM: Novel minimally invasive short-term and long-term peripheral nerve stimulation (PNS) systems have revolutionized targeted treatment of chronic neuropathic pain. We present an international survey of PNS-implanting pain physicians to assess what factors they consider when offering permanent PNS. METHODS: This cross-sectional study consisted of a survey (Qualtrics) that was distributed to PNS-implanting physicians in a device supplier's entire email database on November 13, 2020, with 3 weeks of response time. Physicians' contact information in the form of their email addresses had been previously collected by the supplier upon device distribution with permission to use survey responses for research. RESULTS: Of 2032 database physicians, 40 physicians representing 37 institutions responded to the survey. The most common application of PNS was mononeuropathic pain (57%). The most frequently targeted nerve was the suprascapular nerve (29%). 14% of physicians reported 81-100% of their implants were dual-lead. The representative physicians ranged broadly in their most frequently targeted nerves. Although mononeuropathic pain was the most common indication for PNS, there was still varied response regarding other indications such as CRPS and post-surgical chronic pain. CONCLUSION: In context of a low response rate, identifying such factors can help update the prevailing treatment algorithm for interventional therapies, assist pain physicians in better identifying which patients are the best candidates for PNS, and inform future clinical trial design on PNS efficacy.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Best Practices for Cervical Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate.

Stanford Pragmatiec Effectiveness Comparison (SPEC) protocol: Comparing long-term effectiveness of high-frequency and burst spinal cord stimulation in real-world application.

OBJECTIVES: High-frequency and burst stimulation are newer waveforms that have demonstrated promise compared to traditional tonic spinal cord stimulation (SCS), but more studies are needed to compare their effectiveness. We report the study methods for an ongoing, single center, pragmatic randomized clinical trial to compare the effectiveness of high-frequency and burst SCS in patients with chronic back and/or leg pain. MATERIALS AND METHODS: Participants who are candidates for spinal cord stimulation are enrolled and screened. Participants will be randomly assigned using point-of-care randomization to receive either high-frequency or burst SCS. Data collection will be through Stanford Pain Management Center's learning healthcare system: CHOIR. CHOIR surveys include National Institutes of Health Patient Reported Outcomes Measurement Information System item banks, a body map, questions about pain intensity, pain catastrophizing scale, and questions about patients' pain experience and healthcare utilization. Participants will complete online surveys at baseline and then 1, 3, 6, 12, 18, 24 and 36 months after their device implant. All participants will use our routine process of trial and implant. Reported adverse events are monitored throughout the study. Our primary outcome is change from baseline in pain intensity at 12 months. RESULTS: We hypothesize that high-frequency SCS is more effective than burst SCS in improving pain, physical function and pain interference in participants with chronic low back and/or leg pain. CONCLUSIONS: The pragmatic nature of our proposed trial enables us to recruit a larger participant cohort faster and to follow up these participants longer than currently published clinical trials.

Intrathecal ziconotide for complex regional pain syndrome: seven case reports.

Ziconotide is a nonopioid analgesic currently indicated as monotherapy, but frequently used in combination with opioids, for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of, or whose pain is, refractory to other treatments. There is a paucity of information regarding ziconotide use in patients with complex regional pain syndrome (CRPS). Seven cases in which IT ziconotide was used in patients with CRPS were analyzed. All patients (4 male, 3 female; age range, 14 to 52 years) had experienced inadequate pain relief with multiple conventional and interventional treatments. Three patients received ziconotide monotherapy exclusively; 4 patients received ziconotide monotherapy initially, then combination IT therapy. The mean ziconotide dose was 5.2 mcg/d (range, 0.5 to 13 mcg/d) at initiation and 24.7 mcg/d (range, 0.06 to 146 mcg/d) at the last available assessment. The mean duration of ziconotide therapy was 3.1 years (range, 26 days to 8 years). At ziconotide initiation, the mean visual analog scale (VAS) score was 89.3 mm (range, 75 to 100 mm); VAS scores decreased by a mean of 47.5% (range, 5% to 100%) at last assessment. Of the 5 patients who experienced substantial improvement in pain, edema, skin abnormalities, and/or mobility with ziconotide therapy, 2 have discontinued ziconotide and are pain free. Another patient experienced marked reversal of both edema and advanced skin trophic changes. Adverse events included urinary retention, depression, anxiety, and hallucinations. Adverse events generally resolved spontaneously, with treatment, or with ziconotide discontinuation/dose reduction. Although further studies are required, ziconotide holds promise as an effective treatment for CRPS.

A novel needle-free powder lidocaine delivery system for rapid local analgesia.

OBJECTIVE: To determine the analgesic effect and tolerability of a novel needle-free powder lidocaine delivery system in children undergoing venipuncture. STUDY DESIGN: In this double-blind, placebo-controlled, single-center trial, 306 children age 3 to 18 years were randomized to receive a needle-free powder lidocaine delivery system or matching sham placebo at the back of the hand 2 to 3 minutes before venipuncture. Venipuncture pain was self-reported using the Wong-Baker FACES scale (in 3- to 12-year-olds) and a 100-mm visual analog scale (in 8- to 18-year-olds). Safety was assessed by adverse events, investigator skin site assessments, and children's self-report of the administration comfort of study treatments. Effect sizes were compared by 2-sample t test and Glass's Delta approach. RESULTS: Subjects receiving the needle-free powder lidocaine delivery system exhibited mean pain reductions (effect size) of 33% to 46% relative to sham placebo. Pain reductions were statistically significant for all ages combined and also for the youngest and oldest age strata. Self-reported administration comfort levels were similar in the active system and sham placebo groups. Incidences of adverse events and dermal reactions were low; the most common dermal reaction was mild erythema. CONCLUSIONS: The needle-free powder lidocaine delivery system was well tolerated and provided effective local analgesia when administered 2 to 3 minutes before venipuncture.

Dose-finding, safety, and tolerability study of botulinum toxin type B for the treatment of hyperfunctional glabellar lines.

BACKGROUND: Previous open-label studies have demonstrated that botulinum toxin type B (BTX-B, Myobloc, Solstice Neurosciences) in doses of up to 3,000 U is safe and effective in the treatment of glabellar wrinkles. OBJECTIVE: This double-blind, randomized, placebo-controlled, sequential-dose-escalation study evaluated the safety and tolerability of seven BTX-B doses ranging from 250 to 3,000 U in the treatment of subjects with hyperfunctional glabellar lines. METHODS: Participants received a single intramuscular treatment of either BTX-B or placebo at five facial sites with a 12-week follow-up period. Primary efficacy outcome measure was the Investigator Global Scale score of subject's glabellar lines at rest and at full frown. Safety was evaluated primarily on the occurrence of adverse events (AEs). RESULTS: The investigator scores demonstrated a statistically significant increasing dose-response trend in the percentage of subjects with no lines or mild lines at rest from Weeks 1 to 12 (p=.0420) and at full frown from Weeks 1 to 8 (p<.0001). Fifty-one subjects (36.7%) experienced AEs; the most common AE was headache not otherwise specified, experienced by 19 subjects (13.7%). CONCLUSIONS: BTX-B at doses up to 3,000 U was safe and well tolerated in the treatment of hyperfunctional glabellar lines. Treatment with BTX-B reduced hyperfunctional glabellar lines in subjects, and the duration of action appeared to be related to the dose administered. Further studies using higher doses of BTX-B for treatment of glabellar wrinkles are planned.

A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain.

Safety and efficacy data from a study of slow intrathecal (IT) ziconotide titration for the management of severe chronic pain are presented. Patients randomized to ziconotide (n = 112) or placebo (n = 108) started IT infusion at 0.1 microg/hour (2.4 microg/day), increasing gradually (0.05-0.1 microg/hour increments) over 3 weeks. The ziconotide mean dose at termination was 0.29 microg/hour (6.96 microg/day). Patients' baseline Visual Analogue Scale of Pain Intensity (VASPI) score was 80.7 (SD 15). Statistical significance was noted for VASPI mean percentage improvement, baseline to Week 3 (ziconotide [14.7%] vs. placebo [7.2%; P = 0.036]) and many of the secondary efficacy outcomes measures. Significant adverse events (AEs) reported in the ziconotide group were dizziness, confusion, ataxia, abnormal gait, and memory impairment. Discontinuation rates for AEs and serious AEs were comparable for both groups. Slow titration of ziconotide, a nonopioid analgesic, to a low maximum dose resulted in significant improvement in pain and was better tolerated than in two previous controlled trials that used a faster titration to a higher mean dose.