The Ethical Stewardship of Artificial Intelligence in Chronic Pain and Headache: A Narrative Review.

PURPOSE OF REVIEW: As artificial intelligence (AI) and machine learning (ML) are becoming more pervasive in medicine, understanding their ethical considerations for chronic pain and headache management is crucial for optimizing their safety. RECENT FINDINGS: We reviewed thirty-eight editorial and original research articles published between 2018 and 2023, focusing on the application of AI and ML to chronic pain or headache. The core medical principles of beneficence, non-maleficence, autonomy, and justice constituted the evaluation framework. The AI applications addressed topics such as pain intensity prediction, diagnostic aides, risk assessment for medication misuse, empowering patients to self-manage their conditions, and optimizing access to care. Virtually all AI applications aligned both positively and negatively with specific medical ethics principles. This review highlights the potential of AI to enhance patient outcomes and physicians' experiences in managing chronic pain and headache. We emphasize the importance of carefully considering the advantages, disadvantages, and unintended consequences of utilizing AI tools in chronic pain and headache, and propose the four core principles of medical ethics as an evaluation framework.

Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural history for the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials.

OBJECTIVES: Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS: Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION: There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT: The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS: RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

Long-Term Reductions in Opioid Medication Use After Spinal Stimulation: A Claims Analysis Among Commercially-Insured Population.

Purpose: Chronic, non-cancer pain significantly and negatively impacts patient quality of life. Neuromodulation is a major component of multi-modal interdisciplinary approaches to chronic pain management, which includes opioid and nonopioid medications. In randomized controlled trials, spinal cord stimulation (SCS) has been shown to reduce pain and decrease short-term opioid use for patients. This study sought to evaluate the effect of SCS on longer term opioid and non-opioid pain medication usage among patients over ≥3 years of follow-up. Patients and Methods: Claims analysis was conducted using the Merative™ MarketScan® Commercial Database. Patients aged ≥18 who initiated SCS between 1/1/2010 and 3/31/2021 with ≥1 year of baseline data and ≥3 years of follow-up data were included. Opioid discontinuation, daily dose (DD) reduction, proportion of days covered (PDC), concomitant co-medication with benzodiazepines and/or gabapentinoids, and polypharmacy were evaluated during the baseline and follow-up periods. Adjusted logistic regression was used to evaluate the impact of baseline dosages on discontinuation and dose reduction. Results: During follow-up, 60% of 2,669 SCS patients either discontinued opioid use or reduced opioid DD by at least 20% from baseline; another 15% reduced DD by 1-19%. Logistic regression showed patients with higher baseline dosages were less likely to discontinue opioids completely (odds ratio[OR] 95% confidence intervals[CI]: 0.31[0.18,0.54]) but more likely to reduce their daily dose (OR[CI]: 7.14[4.00,12.73], p<0.001). Mean PDC with opioids decreased from 0.58 (210 of 365 days) at baseline to 0.51 at year 3 (p<0.001). With SCS, co-medication with benzodiazepines decreased from 47.3% at baseline to 30.3% at year 3, co-medication with gabapentinoids reduced from 58.6% to 42.2%, and polypharmacy dropped from 15.6% to 9.6% (all p<0.001). Conclusion: Approximately three-quarters of patients who received SCS therapy either discontinued or reduced systemic opioid use over the study period. SCS could assist in reducing long-term reliance on opioids and other pain medications to treat chronic non-cancer pain.

Application of restorative neurostimulation for chronic mechanical low back pain in an older population with 2-year follow up.

INTRODUCTION: Data on the Medicare-aged population show that older patients are major consumers of low back pain (LBP) interventions. An effective approach for patients with mechanical LBP that has been refractory to conservative management is restorative neurostimulation. The efficacy of restorative neurostimulation has been demonstrated in multiple prospective studies, with published follow-up over 4 years, showing a consistent durable effect. METHODS: To further examine the effect of restorative neurostimulation in an older demographic, data from three clinical studies were aggregated: ReActiv8-B prospectively followed 204 patients, ReActiv8-C study prospectively followed 87 patients and ReActiv8-PMCF prospectively followed 42 patients.Two hundred and sixty-one patients were identified with complete 2-year follow-up and divided into cohorts of equal size based of age quartiles.At 2 years from device activation, patients in either cohort were classified by change in disability (Oswestry Disability Index (ODI)) or change in pain score(NRS/VAS) and assessed as proportion of patients per group at each time point. Additionally, health-related quality of life (HRQoL) (EQ5D-5L) was longitudinally compared with baseline. Differences in proportions were assessed using χ2 and continuous variables by repeated measures analysis of variance. RESULTS: The oldest quartile (n=65) had a median age of 60 (56-82) years compared with the entire population (n=261) who had a median age of 49 (22-82) years. The completer analysis on patients with 2 years of continuous data showed improvement of a 50% in pain was achieved by 62% and 65% and a 15-point ODI improvement in 48% and 60% in the oldest quartile and entire population, respectively. HRQoL (EuroQol 5-Dimension) improved from baselines of 0.568 and 0.544 to 0.763 and 0.769 in the oldest quartile and entire population respectively. All age quartiles improved statistically and clinically over baseline. CONCLUSIONS: This aggregate analysis of three independent studies provides insight into the performance of restorative neurostimulation in an older population. Patients derived significant and clinically meaningful benefit in disability, pain and HRQoL. When compared with a similarly indicated cohort of younger patients, there were no statistically or clinically significant differences.

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.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

The prevalence of opioid medication use among adults in the United States.

OBJECTIVE: More than one in five American adults experiences chronic pain, and numerous approaches can be used to treat chronic pain. Opioid analgesics are commonly used to treat pain though precise estimates of the prevalence of opi-oid analgesic use vary widely. This study sought to determine the prevalence of opioid use for pain among adults in the United States. METHODS: We performed a retrospective analysis of the National Health Interview Survey, a national-level house-hold-based annual survey of self-reported health status of US adults, using a chronic pain module introduced in the 2019 edition. We examined overall rates of opioid medication use for pain and correlates of opioid use using survey-weighted analyses. RESULTS: We found 30.8 million adults (95 percent CI: 29.3-32.3 million), or 12.3 percent (11.8-12.8) of the population, had used opioids for pain in the preceding 12 months, while 9.3 million (8.6-10.0 million), or 3.7 percent (3.5-4.0), had used opioids for chronic pain in the preceding 3 months. Individuals reporting pain every day were more likely to have used opi-oids than those experiencing pain less frequently. Individuals who had tried other methods such as physical therapy and self-management programs were more likely to have used opioids. Individuals who used opioids for pain were more likely to report poorly controlled pain, with 38.0 percent (31.5-45.0) reporting their pain management was "not at all effective." CONCLUSIONS: Opioid use for chronic pain is common and frequently part of a multimodal and multidisciplinary approach.

Higher Pain Sensitivity Predicts Efficacy of a Wearable Transcutaneous Electrical Nerve Stimulation Device for Persons With Fibromyalgia: A Randomized Double-Blind Sham-Controlled Trial.

OBJECTIVES: This study investigated the efficacy of a transcutaneous electrical nerve stimulation (TENS) device (Quell®) for persons with symptoms due to fibromyalgia (FM). MATERIALS AND METHODS: One hundred nineteen (N = 119) subjects were randomly assigned to use an active (N = 62) or sham (N = 57) TENS for three months. All subjects completed baseline questionnaires and were administered quantitative sensory testing (QST). Subjects completed the Patients' Global Impression of Change (PGIC, primary outcome measure) and other mailed questionnaires (secondary outcome measures) at six weeks and three months. RESULTS: The subjects averaged 50.4 ± 13.5 years of age, 93.3% were female, and 79.8% were Caucasian. Most showed benefit from using the TENS, but no differences between groups were found on the primary outcome measure after three months (active 3.87 ± 1.85, sham 3.73 ± 1.80, 95% confidence interval [CI] [-0.60, 0.88], p = 0.707). Those with more hypersensitivity showed most improvement on the PGIC at six weeks (0.22, 95% CI [0.01, 0.43], p = 0.042) and three months (0.20, 95% CI [0.00, 0.41], p = 0.049) and among those with higher sensitivity based on QST, the active TENS group showed the most benefit with TENS compared with the sham treatment (1.20, 95% CI [0.22, 2.18], p = 0.017). No TENS-related serious adverse events were reported. Subjects in the sham group correctly identified their treatment 87.5% of the time, while, surprisingly, subjects in the active group correctly identified their treatment only 17.4% of the time. CONCLUSION: This study found no differences between those who were exposed to maximal-frequency active stimulation or minimal-frequency sham stimulation from a wearable TENS in reducing FM-related symptoms. However, those with greater hypersensitivity showed most benefit from TENS. Additional studies to help determine the role individual differences play in the use of TENS in managing FM-related symptoms are needed.

Effects of Wearable Transcutaneous Electrical Nerve Stimulation on Fibromyalgia: A Randomized Controlled Trial.

PURPOSE: Fibromyalgia is a chronic condition characterized by widespread pain and interference with daily activities. The aim of this study is to assess the benefit of transcutaneous electrical nerve stimulation (TENS) for persons diagnosed with fibromyalgia. PATIENTS AND METHODS: Adults meeting diagnostic criteria for fibromyalgia were randomized in a double-blind trial to receive either an active (n=62) or sham (n=57) wearable TENS device for 3-months. Subjects were classified as having lower or higher pain sensitivity by Quantitative Sensory Testing (QST). Patient Global Impression of Change (PGIC, primary outcome) and secondary efficacy measures including Fibromyalgia Impact Questionnaire (FIQR), Brief Pain Inventory (BPI) and painDETECT questionnaire (PDQ) were assessed at baseline, 6-weeks and 3-months. Treatment effects were determined by a mixed model for repeated measures (MMRM) analysis of the intention-to-treat (ITT) population (N=119). A pre-specified subgroup analysis of pain sensitivity was conducted using an interaction term in the model. RESULTS: No differences were found between active and sham treatment on PGIC scores at 3-months (0.34, 95% CI [-0.37, 1.04], p=0.351) in the ITT population. However, in subjects with higher pain sensitivity (n=60), PGIC was significantly greater for active treatment compared to sham (1.19, 95% CI [0.24, 2.13], p=0.014). FIQR total score (-7.47, 95% CI [-12.46, -2.48], p=0.003), FIQR pain item (-0.62, 95% CI [-1.17, -0.06], p=0.029), BPI Interference (-0.70, 95% CI [-1.30, -0.11], p=0.021) and PDQ (-1.69, 95% CI [-3.20, -0.18], p=0.028) exhibited significant improvements for active treatment compared to sham in the ITT population. Analgesics use was stable and comparable in both groups. CONCLUSION: This study demonstrated modest treatment effects of reduced disease impact, pain and functional impairment from wearable TENS in individuals with fibromyalgia. Subjects with higher pain sensitivity exhibited larger treatment effects than those with lower pain sensitivity. Wearable TENS may be a safe treatment option for people with fibromyalgia. CLINICALTRIALSGOV REGISTRATION: NCT03714425.

Chronic low back pain, bacterial infection and treatment with antibiotics.

The contribution of bacterial infection to chronic low back pain and its treatment with antibiotics have generated considerable controversy in literature. If efficacious, antibiotics have the potential to transform the treatment of chronic low back pain in a significant subset of patients. Some microbiology studies of disc tissue from patients with CLBP have shown that bacteria are present, most likely due to infection, while others conclude they are absent or if found, it is due to surgical contamination. Clinical studies testing the efficacy of oral antibiotics to treat CLBP have either shown that the treatment is efficacious leading to significantly reduced pain and disability or that their effect is modest and not clinically significant. Critical review of the literature on CLBP, bacterial infection and treatment with antibiotics identified five well-designed and executed microbiology studies characterizing bacteria in disc samples that demonstrate that bacteria do infect herniated disc tissue, but that the bacterial burden is low and may be below the limits of detection in some studies. Two randomized, controlled clinical trials evaluating oral antibiotics in patients with CLBP indicate that for certain subsets of patients, the reduction in pain and disability achieved with antibiotic therapy may be significant. In patients for whom other therapies have failed, and who might otherwise progress to disc replacement or fusion surgery, antibiotic therapy may well be an attractive option to reduce the individual suffering associated with this debilitating condition. Additional clinical research is recommended to refine the selection of patients with CLBP caused or complicated by bacterial infection and most likely to respond to antibiotics, to optimize antibiotic therapy to maximize patient benefit, to minimize and manage side effects, and to address legitimate concerns about antibiotic stewardship.

Novel Single Puncture Approach for Simplicity 3 Sacral Plexus Radiofrequency Ablation: Technical Note.

UNLABELLED: Radiofrequency (RF) ablation of the lateral sacral plexus has been used for the treatment of sacroiliac joint pain including as an adjunct to other palliative therapies for the treatment of painful osseous metastasis. The treatment goal is targeted ablation of the dorsal lateral branches of S1-S4. Though several techniques have been described, the Simplicity III (Neurotherm, Middleton, MA) system allows for ablation to be achieved with a single RF probe by utilizing a multi-electrode curved RF probe to create a continuous ablation line across all sacral nerves. In the standard approach, there is sequential introduction of a spinal needle along the desired ablation tract for local anesthesia followed by separate placement of the ablation probe. Though fluoroscopic guidance is utilized, multiple needle passes increase the risk of complication such as bowel perforation or probe insertion through a neural foramen. It may also extend procedure time and increase radiation dose. We illustrate a technique for Simplicity III RF ablation of the dorsal sacral plexus using a modified Seldinger approach for treatment of a patient with sacroiliac joint pain due to osseous renal cell carcinoma metastasis. The desired ablation tract is initially anesthetized via a hollow micropuncture needle. The needle is then exchanged for a peelaway sheath. The RF probe is inserted through the peelaway sheath thus ensuring the probe is placed precisely along the previously anesthetized tract allowing the procedure to be completed using a single percutaneous puncture. We believe that this approach decreases the risks of bowel perforation, patient discomfort as a result of multiple percutaneous punctures, and procedure time. KEY WORDS: Simplicity 3, sacral plexus ablation, image-guided approach, modified Seldinger, chronic sacral pain, thin wall introducer needle.

Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials.

BACKGROUND: The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups. METHODS: Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV). RESULTS: A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone. CONCLUSION: This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone.