Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine.

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PERSPECTIVE: We used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

Fluoroscopy-guided high-intensity focused ultrasound neurotomy of the lumbar zygapophyseal joints: a prospective, open-label study.

OBJECTIVE: The objective of this study is to investigate safety and effectiveness of a fluoroscopy-guided high-intensity focused ultrasound (HIFU) system for thermal ablation of the lumbar medial branch nerves. METHODS: This dual center prospective cohort study enrolled 30 participants with lumbar zygapophyseal joint syndrome. Each participant previously had a positive response to either a single diagnostic analgesic block or radiofrequency ablation (RFA). The primary effectiveness outcome was individual responder rate, defined as a reduction of two points or more on the pain intensity numerical rating scale without an increase in opioid intake, or a reduction in opioid intake without an increase in pain at 6 months after the intervention. The primary safety outcome was procedure-related or device-related adverse events (AEs). Secondary outcome variables included MRI evidence of tissue ablation, Oswestry Disability Index, 12-Item Short Form Health Survey, Brief Pain Inventory, and Patient Global Impression of Change. RESULTS: The individual responder rate was 89.7% at 2 days, 89.7% at 7 days, 72.4% at 14 days, 82.1% at 30 days, 59.3% at 90 days and 82.6% at 180 days. The average Numeric Rating Scale for pain severity decreased from 7.1 at baseline to 3.0 (N=29) after 2 days, 3.0 (N=29) after 7 days, 3.1 (N=29) after 14 days, 3.2 (N=28) after 30 days, 4.3 (N=27) after 90 days, and 3.3 (N=23) after 180 days. All participants tolerated the procedure well with no significant side effects or complications. CONCLUSIONS: Fluoroscopy-guided HIFU neurotomy achieved clinical responses comparable with RFA, and there were no significant device-related or procedure-related AEs. TRIAL REGISTRATION NUMBER: NCT04129034.

Improving access to chronic pain care with central referral and triage: The 6-year findings from a single-entry model.

Background: Despite the established efficacy of multidisciplinary chronic pain care, barriers such as inflated referral wait times and uncoordinated care further hinder patient health care access. Aims: Here we describe the evolution of a single-entry model (SEM) for coordinating access to chronic pain care across seven hospitals in Toronto and explore the impact on patient care 6 years after implementation. Methods: In 2017, an innovative SEM was implemented for chronic pain referrals in Toronto and surrounding areas. Referrals are received centrally, triaged by a clinical team, and assigned an appointment according to the level of urgency and the most appropriate care setting/provider. To evaluate the impact of the SEM, a retrospective analysis was undertaken to determine referral patterns, patient characteristics, and referral wait times over the past 6 years. Results: Implementation of an SEM streamlined the number of steps in the referral process and led to a standardized referral form with common inclusion and exclusion criteria across sites. Over the 6-year period, referrals increased by 93% and the number of unique providers increased by 91%. Chronic pain service wait times were reduced from 299 (±158) days to 176 (±103) days. However, certain pain diagnoses such as chronic pelvic pain and fibromyalgia far exceed the average. Conclusions: The results indicate that the SEM helped reduce wait times for pain conditions and standardized the referral pathway. Continued data capture efforts can help identify gaps in care to enable further health care refinement and improvement.

Contexte: Malgré l'efficacité établie des soins multidisciplinaires dans le traitement de la douleur chronique, des obstacles tels que des délais d'attente prolongés et l'absence de coordination des soins entravent davantage l'accès des patients aux services de santé.Objectifs: Nous décrivons ici l'évolution d'un modèle à entrée unique visant à coordonner l'accès aux soins pour la douleur chronique dans sept hôpitaux de Toronto. Nous examinons également l'effet de ce modèle sur les soins aux patients six ans après sa mise en œuvre.Méthodes: En 2017, un modèle à entrée unique novateur a été mis en place pour orienter les patients souffrant de douleur chronique à Toronto et dans les régions avoisinantes. Les patients sont reçus de manière centralisée, triés par une équipe clinique et un rendez-vous leur est attribué en fonction du degré d'urgence et de l'établissement de soins ou du prestataire le plus approprié.Pour évaluer l'impact du modèle à entrée unique, une analyse rétrospective a été entreprise afin de déterminer les schémas de consultation, les caractéristiques des patients et les temps d'attente pour les demandes de consultation au cours des six dernières années.Résultats: La mise en œuvre d'un modèle à entrée unique a permis de rationaliser le nombre d'étapes du processus de demande de consultation et a conduit à l'élaboration d'un formulaire de demande de consultation normalisé comprenant des critères d'inclusion et d'exclusion communs à tous les sites. Au cours de la période de six ans, le nombre de demandes de consultation a augmenté et le nombre de prestataires uniques a augmenté de 91 %.Les temps d'attente pour les services de traitement de la douleur chronique ont diminué de 299 (±158) jours à 176 (±103) jours. Cependant, certains diagnostics de douleur, comme la douleur pelvienne chronique et la fibromyalgie, dépassent de loin la moyenne.Conclusions: Les résultats indiquent que le modèle à entrée unique a contribué à réduire les temps d'attente pour les affections douloureuses et à normaliser le parcours de consultation. La poursuite des efforts de collecte des données peut aider à recenser les lacunes dans les soins, permettant ainsi une amélioration continue des soins de santé.

Epidural Spinal Cord Stimulation for Spasticity: a Systematic Review of the Literature.

OBJECTIVE: Spasticity is a form of muscle hypertonia secondary to various diseases, including traumatic brain injury, spinal cord injury, cerebral palsy, and multiple sclerosis. Medical treatments are available; however, these often result in insufficient clinical response. This review evaluates the role of epidural spinal cord stimulation (SCS) in the treatment of spasticity and associated functional outcomes. METHODS: A systematic review of the literature was performed using the Embase, CENTRAL, and MEDLINE databases. We included studies that used epidural SCS to treat spasticity. Studies investigating functional electric stimulation, transcutaneous SCS, and animal models of spasticity were excluded. We also excluded studies that used SCS to treat other symptoms such as pain. RESULTS: Thirty-four studies were included in the final analysis. The pooled rate of subjective improvement in spasticity was 78% (95% confidence interval, 64%-91%; I2 = 77%), 40% (95% confidence interval, 7%-73%; I2 = 88%) for increased H-reflex threshold or decreased Hoffman reflex/muscle response wave ratio, and 73% (65%-80%; I2 = 50%) for improved ambulation. Patients with spinal causes had better outcomes compared with patients with cerebral causes. Up to 10% of patients experienced complications including infections and hardware malfunction. CONCLUSIONS: Our review of the literature suggests that SCS may be a safe and useful tool for the management of spasticity; however, there is significant heterogeneity among studies. The quality of studies is also low. Further studies are needed to fully evaluate the usefulness of this technology, including various stimulation paradigms across different causes of spasticity.

End-on versus parallel radiofrequency lesioning for neurotomy of the cervical medial branch nerves: a study protocol of a prospective, randomized, double-blind clinical trial: the "EndPaRL" study.

BACKGROUND: Cervical facet joint disease is a common source of neck pain and its prevalence increases with aging. Conservative multimodal management options (e.g., strengthening of neck muscles, non-steroidal anti-inflammatory medications, massage, and thermal modalities) often fail to relieve pain. Cervical medial branch nerve (CMBN) radiofrequency neurotomy (RFN) is an effective minimally invasive technique for treating chronic neck pain secondary to facet joint disease. An end-on approach for this procedure has been proposed that may be technically easier and require less time while reducing post-procedural discomfort. The protocol presented here is for a study that aims to compare the efficacy of a new end-on approach using multi-tined cannulae, against the conventional parallel technique that employs straight cannulae for RFN of the CMBN in patients with chronic neck pain due to cervical facet joint disease. METHODS: A multicentre randomized, non-inferior, active comparator-controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessor. The study will include 72 adults with chronic neck pain secondary to facet joint disease who are candidates for RFA of the CMBN. Participants will be randomized to either the conventional parallel or the end-on approach in a 1:1 ratio. The intensity of pain and pain-related domains (function, quality of life, sleep, adverse effects of the interventions, analgesic intake) will be measured at 1, 3, 6, and 12 months after the procedure. DISCUSSION: Neck pain secondary to cervical facet joint disease is prevalent and RFA of the CMBN is a validated treatment for relieving it. The conventional parallel technique can be technically challenging, and it can be associated with adverse effects while the newer end-on approach has the potential of being a simpler technique with less adverse effects. This trial will be the first non-inferiority study to compare the clinical efficacy of the end-on approach against the conventional parallel approach for RFN of CMBN in patients with chronic neck pain due to cervical facet joint disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05818774. Registered on April 20, 2023.

Clinical Considerations for Implanted Neurological Devices in Patients Undergoing Hyperbaric Oxygen Therapy: A Case Report and Review of Manufacturer Guidelines.

Patients with implanted medical devices are increasingly referred for hyperbaric oxygen therapy (HBOT), and the safety of exposing some of these devices to hyperbaric environments has not previously been explored. There is a paucity of evidence surrounding the management of implanted neurological devices such as neurostimulators and intrathecal drug delivery (IDD) pumps in the context of HBOT. However, these devices can be expected to harbor unique risks; for example, vacant space in the reservoir of an implanted IDD pump may change in pressure and volume during the compression and decompression phases of HBOT, resulting in a damaged or dysfunctional device. We present the case of a 27-year-old woman with cerebral palsy referred for HBOT to manage a necrotizing soft tissue infection cultured from a dehiscent abdominal wound at the previous implantation site of an intrathecal baclofen pump. An HBOT protocol was ultimately chosen in partnership with the patient and her family, but treatment was not performed due to a paucity of evidence that the implanted IDD pump could safely withstand hyperbaric exposure. In this review, we have synthesized manufacturer recommendations regarding the management of implanted neurological devices before, during, and after HBOT to inform future decision-making in this setting. Among these recommendations, we highlight that neurostimulators should be switched off for the duration of HBOT and implanted pumps should be refilled prior to each treatment session to minimize empty reservoir space.

A Scoping Review of Epidural Spinal Cord Stimulation for Improving Motor and Voiding Function Following Spinal Cord Injury.

Objectives: To identify and synthesize the existing evidence on the effectiveness and safety of epidural spinal cord stimulation (SCS) for improving motor and voiding function and reducing spasticity following spinal cord injury (SCI). Methods: This scoping review was performed according to the framework of Arksey and O'Malley. Comprehensive serial searches in multiple databases (MEDLINE, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, LILACS, PubMed, Web of Science, and Scopus) were performed to identify relevant publications that focused on epidural SCS for improving motor function, including spasticity, and voiding deficits in individuals with SCI. Results: Data from 13 case series including 88 individuals with complete or incomplete SCI (American Spinal Injury Association Impairment Scale [AIS] grade A to D) were included. In 12 studies of individuals with SCI, the majority (83 out of 88) demonstrated a variable degree of improvement in volitional motor function with epidural SCS. Two studies, incorporating 27 participants, demonstrated a significant reduction in spasticity with SCS. Two small studies consisting of five and two participants, respectively, demonstrated improved supraspinal control of volitional micturition with SCS. Conclusion: Epidural SCS can enhance central pattern generator activity and lower motor neuron excitability in individuals with SCI. The observed effects of epidural SCS following SCI suggest that the preservation of supraspinal transmission is sufficient for the recovery of volitional motor and voiding function, even in patients with complete SCI. Further research is warranted to evaluate and optimize the parameters for epidural SCS and their impact on individuals with differing degrees of severity of SCI.

Role of peripheral nerve stimulation in treating chronic neuropathic pain: an international focused survey of pain medicine experts.

Interventional pain management (IPM) options for refractory neuropathic pain (NP) have recently increased with availability of peripheral nerve stimulation (PNS) equipment and expertise. Given a lack of high-quality evidence and guidelines on this topic, we sought to understand the perception of physicians with expertise in treating NP regarding IPM and the role of PNS. We emailed a survey in March 2022 to international NP experts including pain medicine physicians, researchers, and leaders of 11 professional pain societies. No representatives from vendors of PNS systems were included in the design of the survey nor as respondents. Among 24 respondents (67% of those contacted), the distal common peroneal, tibial, and sural nerves were most frequently targeted (60%) with PNS. Persistent postsurgical pain of more than 3 months was the most common indication for PNS (84%). The aggregate NP treatment algorithm in order of median rank was non-opioid medications as first line, IPM including epidural/perineural steroid injections tied with transcutaneous electrical nerve stimulation as second line, pulsed radiofrequency (RF) tied with RF ablation/denervation as third line, temporary then permanent PNS as fourth line, followed by spinal cord stimulation, opioids, cryoablation, botulinum, peripheral nerve field stimulation, intrathecal targeted drug delivery, and others. Before offering PNS, 12 respondents (50%) indicated their preference for trialing non-neuromodulation treatments for 1-3 months. Twenty-two respondents (92%) agreed PNS should be offered early in the treatment of neuropathic pain. The most common barriers to PNS use were cost, lack of high-quality evidence in support of its use, lack of exposure to PNS in training programs, and lack of familiarity with the use of ultrasound guidance. PNS appears to have an increasing role in the treatment of NP but more research is needed on the outcomes of PNS to elucidate its role.

A Scoping Review of Gaps Identified by Primary Care Providers in Caring for Patients with Chronic Noncancer Pain.

Introduction/Aim: Primary care providers (PCPs), who provide the bulk of care for patients with chronic noncancer pain (CNCP), often report knowledge gaps, limited resources, and difficult patient encounters while managing chronic pain. This scoping review seeks to evaluate gaps identified by PCPs in providing care to patients with chronic pain. Methods: The Arksey and O'Malley framework was used for this scoping review. A broad literature search was conducted for relevant articles on gaps in knowledge and skills of PCPs and in their health care environment for managing chronic pain, with multiple search term derivatives for concepts of interest. Articles from the initial search were screened for relevance, yielding 31 studies. Inductive and deductive thematic analysis was adopted. Results: The studies included in this review reflected a variety of study designs, settings, and methods. However, consistent themes emerged with respect to gaps in knowledge and skills for assessment, diagnosis, treatment, and interprofessional roles in chronic pain, as well as broader systemic issues including attitudes toward CNCP. A general lack of confidence in tapering high dose or ineffective opioid regimes, professional isolation, challenges in managing patients with CNCP with complex needs, and limited access to pain specialists were reported by PCPs. Discussion/Conclusions: This scoping review revealed common elements across the selected studies that will be useful in guiding creation of targeted supports for PCPs to manage CNCP. This review also yielded insights for pain clinicians at tertiary centers for supporting their PCP colleagues as well as systemic reforms required to support patients with CNCP.

Introduction/Objectif: Les prestataires de soins primaires, qui fournissent la majeure partie des soins aux patients souffrant de douleur chronique non cancéreuse, font souvent état de lacunes dans leurs connaissances, de ressources limitées et de rencontres difficiles avec les patients dans le cadre de la prise en charge de la douleur chronique. Cet examen de la portée vise à évaluer les lacunes identifiées par les prestataires de soins primaires dans la prestation de soins aux patients souffrant de douleur chronique.Méthodes: Le cadre d'Arksey et O'Malley a été utilisé pour cet examen de la portée. Une vaste recherche documentaire a été menée pour trouver des articles pertinents sur les lacunes dans les connaissances et les compétences des prestataires de soins primaires et dans leur environnement de soins de santé pour la prise en charge de la douleur chronique, avec de multiples dérivés de termes de recherche pour les concepts d'intérêt. Les articles de la recherche initiale ont été examinés pour leur pertinence, ce qui a donné 31 études. L'analyse thématique inductive et déductive a été adoptée.Résultats: Les études incluses dans cette revue reflétaient une variété de devis, de milieux et de méthodes d'étude. Cependant, des thèmes récurrents ont émergé en ce qui concerne les lacunes dans les connaissances et les compétences concernant l'évaluation, le diagnostic, le traitement et les rôles interprofessionnels dans la douleur chronique, ainsi que des problèmes systémiques plus larges, y compris les attitudes à l'égard de la douleur chronique non cancéreuse. Un manque général de confiance dans les traitements opioïdes à dose élevée ou inefficaces, l'isolement professionnel, les difficultés de prise en charge des patients atteints de douleur chronique non cancéreuse ayant des besoins complexes et l'accès limité aux spécialistes de la douleur ont été signalés par les prestataires de soins primaires.Discussion/Conclusions: Cet examen de la portée a révélé des éléments communs aux études sélectionnées qui seront utiles pour guider la création de soutiens ciblés pour les prestataires de soins primaires dans le cadre de la prise en charge de la douleur chronique non cancéreuse. Cette revue a également fourni des informations aux cliniciens de la douleur des centres tertiaires pour soutenir leurs collègues prestataires de soins primaires ainsi que les réformes systémiques nécessaires pour soutenir les patients atteints de douleur chronique non cancéreuse.

Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial.

BACKGROUND: Chronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-D-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion. METHODS: A multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg-1 bolus followed by infusion of 1 mg. kg-1. h-1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusion DISCUSSION: Despite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306899. Registered on April 1, 2022.

Stellate ganglion block for non-pain indications: a scoping review.

INTRODUCTION: Stellate ganglion block (SGB) is performed to relieve head, face, neck, or upper limb pain, and several non-pain indications for performing this block have emerged over the years. To date, there has been no attempt to synthesize evidence on SGB for treating non-pain indications. This scoping review presents a summary of the efficacy and adverse effects of SGB when performed for 6 non-pain indications. METHODS: This scoping review was accomplished through the use of Arksey and O'Malley framework. A literature search was conducted for relevant articles in medical databases to identify publications on SGB and specified study types. Two reviewers independently assessed the risk of bias for randomized controlled trials, nonrandomized comparative studies, and case series. Results were summarized and recommendations were made on the basis of the strength of the available evidence according to the US Preventative Services Task Force grading system. RESULTS: Twenty-four studies (19 randomized controlled trials and 5 nonrandomized studies) were included in this review. On the basis of the evidence, SGB is recommended for obtunding cardiovascular sympathetic stimulation, improving perfusion in limbs, and alleviating menopausal symptoms with a Grade B or C recommendation and a moderate-to-low level of certainty. There was insufficient evidence to recommend SGB for the other indications. CONCLUSIONS: SGB can be considered for obtunding cardiovascular sympathetic stimulation and stress response, reducing vascular tone to improve vascular insufficiency in the limbs and perioperative hemodynamic stability, and alleviating hot flashes in menopause, in conditions refractory to conventional medical management.

Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain. OBJECTIVE: The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain. EVIDENCE REVIEW: Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients' global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized. FINDINGS: Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to -0.61, 95% prediction interval (PI): -0.12 to 0.88, p-value=0.002, I2=55.26, τ2=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: -0.55, 95% CI:-0.69 to -0.19, 95% PI: -1.51 to 0.39, p=0.003, I2=82.49, τ2=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness. CONCLUSIONS: Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy. PROSPERO REGISTRATION NUMBER: CRD42017074255.

North American Neuromodulation Society Educational Curriculum for Intrathecal Drug Delivery Systems Implantation and Management.

OBJECTIVES: Intrathecal drug delivery systems (IDDSs) are used for the treatment of pain and spasticity. A wide range of educational criteria exist for these devices. The North American Neuromodulation Society (NANS) Education Committee developed a comprehensive IDDS curriculum to function as a standard for physician graduate education and assessment through training and into practice. MATERIAL AND METHODS: A multidisciplinary and diverse task force gathered by the NANS Education Committee met in person and virtually over several sessions and developed an IDDS curriculum modeling their previous work on spinal cord stimulation and following the Accreditation Council for Graduate Medical Education (ACGME) Milestones. There were iterative revisions and adaptations to the curriculum, and the final version was approved by the NANS Board of Directors. RESULTS: The curriculum was developed with distinction between implanting physicians and managing physician and physicians who perform both tasks. There is a lateral temporal progression from early learner to practitioner, with advanced learner in the middle. In addition, there is a modular vertical organization that divides the curriculum into the six educational competencies outlined by the ACGME. CONCLUSION: A comprehensive, modular, graduated, and segmented educational curriculum for IDDSs was developed by NANS. We propose the curriculum to be the standard for guidance and assessment of trainees and physicians pursuing training in implanting or managing IDDSs.

Medical Cannabis Use and Inflammatory Cytokines and Chemokines Among Adult Chronic Pain Patients.

Background: Utilizing cannabis as a therapeutic option for chronic pain (CP) has increased significantly. However, data regarding the potential immunomodulatory effects of cannabis in CP patients remain scarce. We aimed at exploring the relationship between cannabis use and inflammatory cytokines and chemokines among a cohort of CP patients. Methods: Adult patients with a CP diagnosis and medical authorization of cannabis were enrolled. Patients completed validated clinical questionnaires and self-reported the effectiveness of cannabis for symptom management. Patients' blood and cannabis samples were analyzed for the presence of four major cannabinoids, two major cannabinoid metabolites, 29 different cytokines/chemokines, and cortisol. The multivariable linear regression model was used to identify cannabis and patient factors associated with immune markers. Results: Fifty-six patients (48±15 years; 64% females) were included, with dried cannabis (53%) being the most common type of cannabis consumed. Seventy percent of products were considered delta-9-tetrahydrocannabinol (Δ9-THC)-dominant. The majority of patients (96%) self-reported effective pain management, and 76% reported a significant decrease in analgesic medication usage (p≤0.001). Compared with males, female patients had higher plasma levels of cannabidiol (CBD), cannabidiolic acid, Δ9-THC, and 11-hydroxy-Δ9-tetrahydrocannabinol but lower concentrations of delta-9-tetrahydrocannabinolic acid and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Females had significantly lower eotaxin levels (p=0.04) in comparison to male patients. The regression analysis indicated that high cannabis doses were related to increased levels of interleukin (IL)-12p40 (p=0.02) and IL-6 (p=0.01), whereas female sex was associated with decreased eotaxin (p≤0.01) concentrations. Blood CBD levels were associated with lower vascular endothelial growth factor (p=0.04) concentrations, and THC-COOH was a factor related to decreased tumor necrosis factor alpha (p=0.02) and IL-12p70 (p=0.03). Conclusion: This study provides further support for the patient-perceived effectiveness of cannabis in managing CP symptoms and reducing analgesic medication consumption. The results suggest a potential sex difference in metabolizing cannabinoids, and the varying immune marker concentrations may support a possible immunomodulatory effect associated with patient sex and cannabis product type. These preliminary findings provide grounds for further validation using larger, well-designed studies with longer follow-up periods.

A Hidden Markov Model reveals magnetoencephalography spectral frequency-specific abnormalities of brain state power and phase-coupling in neuropathic pain.

Neuronal populations in the brain are engaged in a temporally coordinated manner at rest. Here we show that spontaneous transitions between large-scale resting-state networks are altered in chronic neuropathic pain. We applied an approach based on the Hidden Markov Model to magnetoencephalography data to describe how the brain moves from one activity state to another. This identified 12 fast transient (~80 ms) brain states including the sensorimotor, ascending nociceptive pathway, salience, visual, and default mode networks. Compared to healthy controls, we found that people with neuropathic pain exhibited abnormal alpha power in the right ascending nociceptive pathway state, but higher power and coherence in the sensorimotor network state in the beta band, and shorter time intervals between visits of the sensorimotor network, indicating more active time in this state. Conversely, the neuropathic pain group showed lower coherence and spent less time in the frontal attentional state. Therefore, this study reveals a temporal imbalance and dysregulation of spectral frequency-specific brain microstates in patients with neuropathic pain. These findings can potentially impact the development of a mechanism-based therapeutic approach by identifying brain targets to stimulate using neuromodulation to modify abnormal activity and to restore effective neuronal synchrony between brain states.

No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone, and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty.

BACKGROUND: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption. METHODS: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events. RESULTS: Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], -5.6 mg [-2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010). CONCLUSIONS: In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions-local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections-failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty.