Low-Dose Naltrexone Use for Patients with Chronic Regional Pain Syndrome: A Systematic Literature Review.

BACKGROUND: Complex regional pain syndrome is a rare, neuropathic disorder that affects fewer than 200,000 individuals in the United States annually. Current treatments often focus on pain management and fall short of relieving symptoms of pain and dystonia in patients. OBJECTIVE: The goal of this systematic qualitative review is to evaluate the evidence for the use of low-dose naltrexone in the treatment of chronic pain syndromes. STUDY DESIGN: This is a systematic review. METHODS: PubMed, Embase, and Web of Science were searched for articles containing the keywords "low-dose naltrexone" AND ("pain" OR "chronic pain" OR "fibromyalgia" OR "complex regional pain syndrome" OR "neuropathic pain" OR "nociceptive pain") between 1950 and July 17, 2020. A total of 30 publications were systematically reviewed. Exclusion criteria were articles that were unavailable in English, focused on acute pain only, and evaluated only animal models. Case studies were included for the purposes of our qualitative review. RESULTS: Out of 29 articles, we reviewed 11 prospective studies, 10 case studies, 3 systematic reviews, 2 retrospective studies, 2 simulation models, and one combination study. Articles focused on chronic pain syndromes as well as painful rheumatologic disorders and neurological disorders. We found that low-dose naltrexone treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep disturbances. LIMITATIONS: Due to the limited number of available articles focusing on the treatment of complex regional pain syndrome with low-dose naltrexone, the majority of studies analyzed focused on other chronic pain syndromes. CONCLUSIONS: There is a need for additional prospective and interventional studies addressing the use of low-dose naltrexone in the treatment of complex regional pain syndrome symptoms.

COVID-19 and the Opioid Epidemic: Two Public Health Emergencies That Intersect With Chronic Pain.

The COVID-19 pandemic has affected the entire world and catapulted the United States into one of the deepest recessions in history. While this pandemic rages, the opioid crisis worsens. During this period, the pandemic has resulted in the decimation of most conventional medical services, including those of chronic pain management, with the exception of virtual care and telehealth. Many chronic pain patients have been impacted in numerous ways, with increases in cardiovascular disease, mental health problems, cognitive dysfunction, and early death. The epidemic has also resulted in severe economic and physiological consequences for providers. Drug deaths in America, which fell for the first time in 25 years in 2018, rose to record numbers in 2019 and are continuing to climb, worsened by the coronavirus pandemic. The opioid epidemic was already resurfacing with a 5% increase in overall deaths from 2018; however, the preliminary data show that prescription opioid deaths continued to decline, while at the same time deaths due to fentanyl, methamphetamine, and cocaine climbed, with some reductions in heroin deaths. The health tracker data also showed that along with an almost 88% decline in elective surgeries, pain-related prescriptions declined 15.1%. Despite increases in telehealth, outpatient services declined and only began returning towards normal at an extremely slow pace, accompanied by reduced productivity and increased practice costs. This review, therefore, emphasizes the devastating consequences of concurrent epidemics on chronic pain management and the need to develop best practice efforts to preserve access to treatment for chronic pain.

Methodology for Evidence Synthesis and Development of Comprehensive Evidence-Based Guidelines for Interventional Techniques in Chronic Spinal Pain.

BACKGROUND: The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. OBJECTIVE: To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. METHODS: A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations. RESULTS: Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews. LIMITATIONS: Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques. CONCLUSION: This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.

Steroid Distancing in Interventional Pain Management During COVID-19 and Beyond: Safe, Effective and Practical Approach.

BACKGROUND: Since the late 1940s, corticosteroids have been a mainstay class of agents in multiple interventional techniques and intra-articular injections. Exogenous glucocorticoids are structurally and pharmacologically similar to the endogenous hormones. As such, multiple actions of corticosteroids are exhibited, including those of anti-inflammatory and immunosuppressive effects. Epidural injections, with or without steroids, have been extensively used throughout the world. There are reports of epidural injections starting in 1901, with steroids being added to the local anesthetic since 1952, when steroids were administered into the sacral foramen. PURPOSE: Due to the extensive side effects of steroids in various injections, some have proposed limiting their use in epidurals and intraarticular injections. With the COVID-19 pandemic, the multiple side effects of the steroids have elevated the level of concern and recommendations have been made to utilize local anesthetic alone or the lowest dose of steroids. Fashioned from common expressions of the day, the term "steroid distancing" began to be used and proposed for intraarticular injections of the knee. Consequently, we sought to evaluate the evidence and feasibility of steroid distancing in interventional pain management. METHODS: This focused review of local anesthetics and steroids utilized in interventional pain management for epidural injections, peripheral nerve blocks, and intraarticular injections by multiple database searches. This is a focused narrative review and not a systematic review. Consequently, evidence synthesis was not performed traditionally, but was based on an overview of the available evidence. RESULTS: No significant difference was identified based on whether steroids are added to local anesthetic or not for epidural as well as facet joint injections. However, there was not enough evidence to compare these two groups for peripheral intraarticular injections. LIMITATIONS: The present review is limited by the paucity of literature with bupivacaine alone or bupivacaine with steroids local anesthetic alone or with steroids of intraarticular injections of knee, hip, shoulder and other joints, and intraarticular facet joint injections. CONCLUSION: This review shows an overall lack of significant difference between lidocaine alone and lidocaine with steroids in epidural injections. However, available evidence is limited for bupivacaine alone or with steroids. Evidence is also not available comparing local anesthetic alone with steroids for facet joint or peripheral joint intraarticular injections. Thus, it is concluded that local anesthetic with lidocaine may be utilized for epidural injections, with appropriate patient selection and steroids reserved for non-responsive patients with local anesthetic and with significant radiculitis.

Ohio Response to COVID-19 and Its Impact on Interventional Pain Management Practices.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered daily living and medical care for Ohio residents and the practice of medicine for the interventional pain management physician. As a state, Ohio tends to be demographically representative of the broader US population. OBJECTIVE: Reviewing the efforts deployed by Ohio to flatten the COVID-19 infection curve and reduce the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important component of determining optimal procedures for mitigating the effects of the COVID-19 pandemic. METHODS: Over the course of several announcements and orders during the months of March and April, new policies were put into place to prevent COVID-19 transmission, which included efforts to facilitate social distancing and ensure the health care system could manage the number of COVID-19 cases at peak infection rate. Efforts directed toward medical providers included delay of elective procedures, expansion of telehealth options, and new temporary guidance for prescribing controlled substances. RESULTS: The Ohio COVID-19 containment approach resulted in a substantial reduction in COVID-19 cases compared with early models of disease spread, and the state has begun a phased reopening. Continued vigilance in applying social distancing and infection control measures will be a critical component of preventing or reducing the impact of a second wave of COVID-19 in Ohio. LIMITATIONS: A narrative review with paucity of literature.

Outcomes of a Multicenter, Prospective, Crossover, Randomized Controlled Trial Evaluating Subperception Spinal Cord Stimulation at ≤1.2 kHz in Previously Implanted Subjects.

OBJECTIVE: The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain. METHODS: WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference. RESULTS: The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%). DISCUSSION: Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved.

Treatment of Occipital Neuralgia by Thermal Radiofrequency Ablation.

BACKGROUND: Occipital neuralgia is an uncommon disorder characterized by severe pain involving the posterior scalp in the distribution of the greater and lesser occipital nerves. In cases refractory to pharmacotherapy, invasive treatment options may be warranted. The aim of the present study was to examine the effects of thermal radiofrequency ablation (TRF) on occipital neuralgia. We hypothesized that this procedure would result in long-term pain relief. METHODS: All patients who underwent TRF of the greater and lesser occipital nerves between January 1, 2013 and March 23, 2016 were identified. Medical records were reviewed for preprocedure pain score, 1-month postprocedure pain score, patient-defined percent pain relief according to the visual analog scale (on which zero equals no pain and 10 represents the worst pain imaginable), and length of pain relief. The primary outcomes were the differences between preprocedure and 1-month postprocedure pain scores (mean change from baseline), percent pain relief, and patient-reported length of relief. RESULTS: A total of 50 patients were identified; 4 patients were excluded because of insufficient data as a result of loss to follow-up. A significant difference was found between preprocedure and postprocedure patient-reported pain scores (6.7 vs 2.7, respectively; P < 0.001), equating to a mean reduction in pain scores 1-month postprocedure of 4.0 ± 3.3. The mean patient-defined percent pain relief was 76.3% ± 25.0%. The mean patient-reported length of relief was 6.5 ± 5.1 months. CONCLUSION: This study suggests that TRF may reduce pain scores for approximately 6 months.

Lack of electrical interference between spinal cord stimulators and other implanted electrical pulse devices.

Spinal cord stimulators (SCSs) have been used for decades to treat chronic pain. SCSs are often used to treat patients with chronic back pain caused by failed back surgery syndrome, patients with complex regional pain syndrome, or individuals who are not candidates for surgery. SCSs are a relative contraindication in patients with another electrical pulse device. We present 3 patients who received SCS despite having another implant in place. There was no interaction between devices. The first case was a patient with failed back surgery syndrome who had an implantable cardiac defibrillator and an SCS implant. The second case was a nonsurgical candidate with a pacemaker who received an SCS to help with lower back pain due to an occupational injury. The third case was a patient with complex regional pain syndrome and a bladder stimulator with a previous SCS who received a revision to help manage the pain. In all these patients, pain scores significantly improved after the trial.

Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series.

INTRODUCTION: Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. Our series aimed at testing the efficacy of spinal cord stimulators (SCSs) in treating resistant painful peripheral neuropathy. CASE PRESENTATIONS: Case 1: A 79-year-old man presented to our clinic with long-standing history of painful peripheral diabetic neuropathy resistant to conservative management. After failure of all possible modalities, we offered the patient an SCS trial that was very successful, and we proceeded with the permanent implant that continued to help with his pain and allowed the patient to wean down his medications. Case 2: A 60-year-old man presented with chronic peripheral neuropathy secondary to HIV, patient failed all conservative and procedural management. Patient then had an SCS trial that relieved his pain significantly. Unfortunately, we did not proceed with the implant due to deterioration of the patient general health. Case 3: A 39-year-old woman presented with painful peripheral neuropathy secondary to chemotherapy for breast cancer. After failure of medication management and procedures, patient had a SCS trial that improved her pain and we then proceeded with performing the permanent implant that controlled her pain. CONCLUSION: We presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation.

Effective Management of Trigeminal Neuralgia by Neurostimulation.

BACKGROUND: Treatment of trigeminal neuralgia can be challenging for many physicians; patients who do not respond to conventional treatments and traditional surgical approaches often continue to suffer with pain. The peripheral nerve stimulator (PNS) has been used to treat many chronic pain conditions, but few reports exist about its use to treat trigeminal neuralgia. CASE REPORT: We present the case of a patient with trigeminal neuralgia resistant to conventional techniques of pain management. Conservative pain management was attempted but was ineffective. As a result, a PNS was placed with minimally invasive surgery. Pain scores were recorded before and after the procedure, and the patient reported complete resolution of her pain. CONCLUSION: PNS implantation can be a safe and effective method to treat trigeminal neuralgia. More research is needed to define its mechanism of action.