Preoperative psychological stress is a highly prevalent but mostly underrecognized factor influencing perioperative physiology and postoperative outcomes. This narrative review synthesizes current evidence on the known mechanisms connecting preoperative stress to adverse surgical outcomes, with particular emphasis on HPA axis functioning, cortisol dynamics, inflammatory signaling and pain modulation. Elevated preoperative anxiety affects a substantial proportion of surgical patients and is consistently associated with increased analgesic and anesthetic requirements, higher postoperative pain intensity, greater risk of chronic postsurgical pain, neuropsychiatric complications, metabolic dysregulation and postoperative infections. Stress-related elevations in cortisol and pro-inflammatory cytokines, particularly interleukin-6, appear to mediate these effects through interactions with immune, metabolic, and central nervous system pathways. Stress-related pain modulation is reflected not only in experimental models but also in clinically measurable outcomes, underscoring its relevance for perioperative care. Despite growing recognition of these associations, standardized strategies for integrating stress assessment and biomarkers into perioperative risk stratification remain limited. Given that preoperative stress is potentially modifiable, targeted psychological, analgesic, and metabolic interventions may represent valuable opportunities to improve recovery, reduce complications, and prevent pain chronification.

Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments occurring across the surgical period and are associated with significant morbidity, delayed recovery, and reduced quality of life. Although established risk factors include advanced age, cardiovascular disease, and preexisting cognitive impairment, the contribution of mood disorders to PND susceptibility remains incompletely understood. This review systematically examines the neurobiological overlap between mood disorders, particularly major depressive disorder (MDD) and bipolar disorder, and PND, with emphasis on shared biomolecular mechanisms. We identify convergent pathophysiologic pathways including hypothalamic-pituitary-adrenal (HPA) axis dysregulation, chronic neuroinflammation, NF-κB-mediated cytokine signaling, microglial priming, tryptophan-kynurenine pathway dysregulation, and brain-derived neurotrophic factor (BDNF) suppression. These mechanisms collectively suggest that patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction. Recognition of mood disorders as modifiable perioperative vulnerability states may inform preoperative risk stratification, guide anesthetic and analgesic management, and support the development of targeted interventions to reduce postoperative cognitive complications and improve surgical outcomes.

Chronic pain, sleep disturbances, and mental health disorders such as anxiety and depression disorders frequently co-occur, forming a self-reinforcing cycle that impairs daily functioning and quality of life. Chronic pain is driven by peripheral and central sensitization, the latter sustained by reciprocal microglial–astrocytic crosstalk and maladaptive neuroplasticity. Poor sleep amplifies pain through inflammation and circadian disruption. Imbalances in serotonin, dopamine, and norepinephrine, together with limbic alterations and HPA axis dysregulation, contribute to comorbid anxiety and depression. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), NF-κB-driven neuroinflammation, and mitochondrial oxidative stress serve as key molecular links. Building on previous evidence, this review presents an updated triadic, mechanism-based framework describing the reciprocal reinforcement among chronic pain, sleep disturbances, and anxiety and depressive disorders. Consequently, therapeutic strategies targeting inflammatory cytokines, microglial and astrocytic activation, neurotransmitter imbalance, and psychological dysfunction may help address these shared neuroimmune and neuroplastic mechanisms underlying these interconnected disorders.

BACKGROUND:Recent analysis of epidural procedure utilization has demonstrated significant shifts over the past 25 years. Utilization increased substantially until 2004, continued with modest growth through 2011, and then gradually declined through 2019 among the Medicare population. Influences from the COVID-19 pandemic, the Affordable Care Act (ACA), and economic pressures have continued to contribute to declining utilization patterns. OBJECTIVE:The present investigation provides an updated evaluation of epidural procedure utilization for chronic pain management in the U.S. Medicare population, focusing on the time periods of 2000 to 2010, 2010 to 2019, and 2019 to 2024. STUDY DESIGN:A retrospective cohort study evaluating utilization patterns and variables for epidural injections in the fee-for-service (FFS) traditional Medicare population in the U.S. from 2000 to 2024. METHODS:A retrospective longitudinal analysis of Medicare Part B data from 2000 through 2024 was completed. Epidural injection services included cervical/thoracic and lumbar/caudal interlaminar injections, and cervical/thoracic and lumbar/sacral transforaminal injections, identified using procedure codes in the study database. A procedure or service represented all interventions performed during a treatment episode, incorporating add-on codes and bilateral services. Episodes were defined as one unit regardless of bilateral or additional services, reflecting the number of times patients received treatment. Utilization was assessed through counts, rates per 100,000 beneficiaries, geometric mean changes, and percent changes across key intervals (2000-2010, 2010-2019, 2019-2024). Trends by provider's specialty and place of service were also evaluated. RESULTS:From 2000 to 2010, services, episodes, and rates per 100,000 beneficiaries increased 144.3%, 126.1%, and 103%. From 2010 to 2019, this pattern shifted to declining utilization, with reductions of 9.5% in services, 0.4% in episodes, and 9% in rates per 100,000. From 2019 to 2024, procedural rates declined 13%, episodes declined 22.6%, and episode rates declined 11.9%, corresponding to average annual reductions of 2.8%, 4.3%, and 2.6%.Comparative analysis showed that from 2000 to 2010, interlaminar epidural rates increased 43.8%, whereas transforaminal epidural rates increased 579.1%. From 2010 to 2019, interlaminar rates declined 18.4%, while transforaminal rates increased 5%. From 2019 to 2024, interlaminar rates declined 14.6% compared to 8.7% for transforaminal procedures. By 2024, interventional pain specialists performed over 92% of all epidural injections, while other specialties showed decreasing participation. A continued shift toward office settings and ambulatory surgery centers (ASCs) was also observed. LIMITATIONS:The study includes data only through 2024 and is limited to the FFS Medicare population, excluding Medicare Advantage beneficiaries who accounted for 54% of Medicare enrollment by 2024. Limitations inherent to retrospective claims data also apply. CONCLUSION:Epidural injection utilization has shifted substantially over the last 25 years, driven by changes in clinical practice, regulatory and economic influences, and pandemic-related disruptions. The increasing concentration of procedure utilization among interventional pain specialists, together with the continued expansion of transforaminal techniques, underscores the progressive specialization and refinement of interventional pain management within the Medicare population.

Chronic pain is a highly prevalent and disabling condition with a well-documented female predominance in incidence, severity and persistence. These sex differences are driven by sexually dimorphic neuroimmune mechanisms rather than psychosocial factors alone. This systematic review was conducted to comprehensively synthesize human clinical and translational evidence on sex-specific neuroimmune and glial cell pathways underlying chronic pain. Scientific literature was systematically searched from database inception to December 2025 across multiple biomedical databases to identify relevant clinical and translational studies. Across pain conditions, convergent evidence demonstrated that chronic pain mechanisms diverge by sex at cellular and molecular levels. Male-predominant pathways were characterized by microglial activation, particularly P2X4 receptor-mediated signaling and brain-derived neurotrophic factor-dependent neuronal disinhibition, supported by neuroimaging, transcriptomic, and pharmacological data. In contrast, female-predominant mechanisms involved adaptive immune processes, including CD4+ and CD8+ T cell infiltration, pannexin-1-dependent leptin release, chemokine signaling, and astrocyte-mediated neuroimmune crosstalk. Sex-specific cytokine and chemokine profiles, differential glial activation patterns, and divergent neuroimmune-endocrine interactions further distinguished pain pathways between males and females. Despite consistent mechanistic trends, substantial heterogeneity within each sex, limited sex-stratified power in many studies, and variability in outcome measures constrained quantitative synthesis and generalizability. The findings indicate that chronic pain is not a unitary disorder but rather a collection of mechanistically distinct conditions shaped by biological sex. These results highlight the limitations of sex-neutral therapeutic strategies and support the development of precision medicine approaches incorporating sex-informed neuroimmune biomarkers and mechanism-matched interventions. Future studies should prioritize adequately powered sex-stratified analyses, integration of neuroimmune biomarkers and clinical trial designs capable of detecting sex-by-treatment interactions.

Postoperative cardiovascular complications remain a leading cause of morbidity and mortality after noncardiac surgery, yet current risk models do not incorporate psychosocial stress. With over 300 million noncardiac surgeries performed annually worldwide and a substantial burden of perioperative cardiovascular complications, preoperative chronic stress is increasingly recognized as a potentially modifiable risk factor. Chronic stress produces HPA axis dysregulation, glucocorticoid resistance, sympathetic activation, inflammation, endothelial dysfunction, and hypercoagulability. These pathways overlap with the mechanisms underlying perioperative myocardial injury, arrhythmogenesis, and venous thromboembolism. Prospective data demonstrated that preoperative psychological distress independently predicted 30-day cardiovascular complications and 1-year mortality after noncardiac surgery. Allostatic load studies in noncardiac surgery patients showed that high preoperative physiological burden was associated with up to twofold increases in postoperative mortality and elevated rates of myocardial infarction and venous thromboembolism. Epidemiological evidence further supports that anxiety and depression independently increase cardiovascular risk. Converging evidence suggests that preoperative psychological distress is a relevant perioperative cardiovascular risk factor. However, no randomized controlled trial has evaluated whether targeted preoperative stress reduction can decrease postoperative cardiovascular events, representing a critical gap warranting prospective investigation.

Chronic pain is one of the most common and disabling complications of chronic kidney disease (CKD), yet it is almost exclusively viewed as a consequence of declining kidney function. This perspective overlooks the possibility that chronic pain itself may influence the biological processes driving CKD progression. Chronic pain is being recognized as a systemic disorder characterized by sustained neuroimmune activation, inflammation, oxidative stress, endothelial dysfunction, autonomic imbalance, mitochondrial impairment and maladaptive behavioral changes. These same mechanisms are also central to progressive kidney injury, raising the possibility that persistent pain may reinforce established pathogenic pathways rather than simply accompany them. We propose a conceptual framework in which chronic pain functions as a disease modifier capable of amplifying the biological and clinical processes that contribute to CKD progression. Although this hypothesis does not imply that chronic pain directly causes CKD or that pain management is inherently renoprotective, it provides a biologically plausible rationale for investigating whether pain contributes to disease progression beyond serving as a marker of disease severity. Exploring this possibility may broaden current concepts of CKD progression and identify new directions for mechanistic, translational and clinical research.

Exercise-induced hypoalgesia (EIH) illustrates how physical activity can reshape the biology of pain while simultaneously influencing the systems that regulate stress. Acute and repeated exercise can reduce pain sensitivity in healthy individuals and in some chronic pain populations, yet the magnitude and consistency of these effects vary substantially across individuals, diagnoses, and exercise protocols. This variability suggests that EIH is not a uniform response, but an adaptive multisystem process shaped by neural, immune, endocrine, metabolic, musculoskeletal, and psychosocial factors. This narrative review synthesizes evidence linking pain modulation and stress regulation across biological scales. Exercise engages descending pain modulatory circuits involving the periaqueductal gray, rostral ventromedial medulla, and spinal dorsal horn, while also influencing endogenous opioid, endocannabinoid, serotonergic, and noradrenergic signaling. These pathways are relevant not only to nociceptive inhibition, but also to affective regulation, hypothalamic-pituitary-adrenal axis activity, autonomic balance, and perceived stress. In parallel, exercise-related neuroimmune changes, including modulation of microglial activity, cytokine signaling, and myokine release from skeletal muscle, may connect peripheral metabolic activity with central mechanisms of pain and stress adaptation. Importantly, the evidence supporting these mechanisms differs in strength: some findings derive from human experimental and clinical studies, whereas others are supported mainly by preclinical or translational research. By distinguishing direct evidence from mechanistic inference, this review highlights how exercise may support hypoalgesia, stress resilience, and functional recovery, while also emphasizing the need for biomarker-informed, personalized exercise strategies in chronic pain management.

BACKGROUND:Chronic axial spinal pain is a major cause of disability. The literature shows that expenditures related to low back and neck pain and other musculoskeletal disorders continue to rise, not only due to disability but also due to increasing healthcare costs, accounting for the highest expenditure among various disease categories. Based on current evidence utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been identified as potential sources of spinal pain. Therapeutic facet joint interventional modalities for axial spinal pain include radiofrequency ablation, therapeutic facet joint nerve blocks, and therapeutic intraarticular injections. OBJECTIVE:The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency ablation as a therapeutic modality in managing chronic axial spinal pain of facet joint origin. STUDY DESIGN:A systematic review and meta-analysis of randomized controlled trials (RCTs) utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. METHODS:The available literature on radiofrequency ablation in axial spinal pain was reviewed. The quality assessment criteria utilized included the Cochrane review criteria to assess risk of bias and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials. The evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. The level of evidence was determined based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V.A comprehensive literature search of multiple databases from 1966 to June 2025, including manual searches of the bibliographies of relevant review articles, was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into both qualitative and quantitative analyses. OUTCOME MEASURES:The primary outcome measure was the proportion of patients achieving significant pain relief and functional improvement of greater than 50% for at least 6 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS:This assessment identified 17 RCTs, including 14 high-quality and 3 moderate-quality studies based on Cochrane criteria, and 11 high-quality and 6 moderate-quality studies based on IPM-QRB criteria. Based on the GRADE assessment, 8 trials demonstrated at least moderate levels of impact and certainty, whereas 7 trials showed low impact with low certainty, and 2 trials demonstrated very low impact and certainty. LIMITATIONS:Despite the availability of multiple studies, the relative paucity of high-quality literature remains a major limitation. CONCLUSION:Based on this systematic review and meta-analysis of 17 RCTs, the evidence is Level II with moderate certainty and a moderate strength of recommendation for the use of radiofrequency ablation in managing chronic axial spinal pain of facet joint origin.

BACKGROUND:Chronic axial spinal pain is one of the leading causes of disability. The literature demonstrates that expenditures for low back and neck pain continue to rise, not only in parallel with increasing disability, but also with escalating healthcare costs, accounting for the highest spending among multiple disease categories. Based on current evidence utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been identified as potential sources of spinal pain. STUDY DESIGN:A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. OBJECTIVE:To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. METHODS:Methodological quality of the included studies was assessed using the Quality Appraisal of Reliability Studies (QAREL) instrument. Only diagnostic accuracy studies meeting at least 50% of the predefined inclusion criteria were included in the analysis.The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Levels of evidence were classified using a modified best evidence synthesis, ranging from Level I to Level V.Data sources included relevant literature identified through PubMed and other electronic searches published from 1966 through September 2025, Cochrane reviews, and manual searches of the bibliographies of primary and review articles. OUTCOME MEASURES:Eligible studies were required to use placebo-controlled or comparative local anesthetic blocks. A positive diagnostic standard was defined as at least 50% pain relief from baseline scores along with the ability to perform previously painful movements. RESULTS:The available evidence demonstrated Level I for lumbar facet joint nerve blocks, based on 18 studies employing dual diagnostic blocks, demonstrating 75% to 80% pain relief, with an average prevalence of 16% to 45% and estimated or presumed false-positive rates of 25% to 50%.Evidence for the diagnosis of cervical facet joint pain using cervical facet joint nerve blocks is Level II, derived from 12 controlled diagnostic accuracy studies, showing substantial heterogeneity and internal inconsistency. Reported prevalence ranged from 36% to 67% with ≥ 80% pain relief and estimated or presumed false-positive rates of 26% to 63%.The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II, based on 3 studies using dual diagnostic blocks, demonstrating 80% or greater pain relief, with prevalence ranging from 34% to 48% and estimated or presumed false-positive rates ranging from 42% to 58%. LIMITATIONS:Limitations of this systematic review include the limited number of studies involving the thoracic spine, ongoing debate regarding the appropriate reference standard, challenges in determining false-positive rates, concerns regarding the appropriateness of diagnostic blocks, the scarcity of recent publications, and issues related to clinical utility. CONCLUSION:There is Level I evidence for the diagnostic accuracy of lumbar facet joint nerve blocks and Level II evidence for cervical and thoracic facet joint nerve blocks in the evaluation of chronic spinal pain.

BACKGROUND:The use of facet joint interventions for spinal pain management increased rapidly between 2000 and 2010, followed by slower growth from 2010 to 2019. Post-COVID analyses demonstrated a marked decline in facet joint interventions despite an increasing prevalence of chronic pain among traditional Medicare beneficiaries after 2019, together with multiple contributing factors over time, including enactment of the Affordable Care Act, COVID-19, the Inflation Reduction Act, and other influences. OBJECTIVE:This study aims to update and analyze utilization patterns of facet joint interventions for chronic pain management in the U.S. traditional Medicare population across multiple periods from 2000 to 2024. STUDY DESIGN:A retrospective cohort study evaluating utilization trends and influencing factors for facet joint interventions in the fee-for-service (FFS) traditional Medicare population in the United States from 2000 to 2024. METHODS:Data were derived from the Centers for Medicare & Medicaid Services (CMS) physician/supplier procedure summary database (2000-2024). Utilization rates per 100,000 Medicare beneficiaries, percentage of change, and geometric average changes were calculated. RESULTS:Facet joint intervention utilization increased rapidly from 2000 to 2010 (15.5% annually), slowed from 2010 to 2019 (4.2% annually), and declined from 2019 to 2024 (-6.1% annually). Episodes followed similar patterns but declined less steeply than procedures (-6.7% vs. -27.1%). By 2024, service rates had returned to approximately 2012 levels (5,016 vs 5,046 per 100,000 beneficiaries). From 2000 to 2010, lumbar and cervical/thoracic facet joint blocks and radiofrequency ablation procedures increased substantially (13.5%-24.6% annually), followed by slower growth from 2010 to 2019 (2.8%-11.0%), a sharp pandemic-related decline from 2019 to 2020 (10.6%-17.4%), and partial recovery with modest growth or stabilization through 2024. Between 2019 and 2024, the episode ratio of facet joint nerve blocks to radiofrequency ablation declined from 1.9 to 1.7 for lumbar procedures and from 2.4 to 2.0 for cervical procedures, attributed to the mandatory radiofrequency policy. Interventional pain-related specialties accounted for the majority of facet joint procedures, increasing their share from 87.3% in 2010 to 95% by 2024, while surgical specialties declined from 4.8% to 2.0%. During the same period, the site of service shifted modestly from office settings (50.7% to 48.8%) and hospital outpatient departments (HOPD) (declining to 20.5%) toward ambulatory surgery centers (ASCs) (25.6% to 30.6%). These findings reflect increasing specialization, recent reductions in treatment intensity, and the influence of policy changes, Medicare Advantage shifts, and broader system pressures on pain management. LIMITATIONS:The analysis was limited to the FFS traditional Medicare population and data availability through 2024, excluding utilization patterns for Medicare Advantage Plans, which covered 54% of Medicare enrollees in 2024. As with other retrospective claims-based studies, inherent limitations related to coding and administrative data apply. CONCLUSION:This retrospective analysis demonstrates a substantial decline in facet joint intervention episodes, with an overall reduction of 6.7% per 100,000 Medicare beneficiaries and an annual decline rate of 1.4% for episodes from 2019 to 2024. In contrast, services or procedures declined more markedly, with an overall reduction of 27.1% and an annual decline rate of 6.1% per 100,000 Medicare beneficiaries.

BACKGROUND:Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain. OBJECTIVE:To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS:A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and the Agency for Healthcare Research and Quality (AHRQ) methods for grading strength of recommendations. The evidence review included existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies evaluating the effectiveness and safety of facet joint interventions in chronic pain management.In the development of consensus statements and guidelines, a modified Delphi technique was utilized to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approval of specific guideline statements. Each panelist was permitted to suggest revisions to guideline wording and provide additional qualifying remarks or comments regarding implementation of the guidelines in clinical practice. To achieve consensus and inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without a primary conflict of interest. RESULTS:A total of 48 authors participated in the development of these guidelines, of whom 39 participated in the voting process. A total of 37 recommendations were developed, with 100% acceptance for all items. The Summary of Recommendations is presented separately. These recommendations addressed diagnostic, therapeutic, and special considerations related to facet joint interventions. For diagnostic and therapeutic interventions, the level of evidence ranged from II to III, with moderate to strong recommendations. For special considerations and safety assessments, the level of evidence ranged from II to V. The evidence provided recommendations regarding diagnosis, treatment, sedation, concurrent antithrombotic therapy, and precautions required in special clinical circumstances. LIMITATIONS:The limitations of these guidelines include a paucity of high-quality studies in some aspects of diagnosis and therapy. CONCLUSION:These guidelines for facet joint interventions were developed through a comprehensive review of the literature, including methodologic quality assessment and determination of the level of evidence and strength of recommendations. DISCLAIMER:These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

BACKGROUND:Ilioinguinal neuralgia is a frequent cause of pain in the lower abdomen, genitals, and upper thighs and is commonly caused iatrogenically. Patients with ilioinguinal neuralgia often have a history of surgical interventions such as hernia repairs, appendectomies, or hysterectomies. OBJECTIVES:The objective of this narrative literary review is to catalog and provide an organized level of evidence for the available interventions for treating ilioinguinal neuralgia. METHODS:Research databases, including PubMed, CINAHL and Google Scholar, were searched for characterization, diagnosis, and treatment of ilioinguinal neuralgia. The included results comprised case studies, randomized trials, and meta-analyses. Interventions were organized from least to most invasive and sorted into 3levels (A-C). Level A consisted of data derived from multiple randomized clinical trials or meta-analyses. Level B consisted of data derived from single randomized trials or nonrandomized studies. Level C was composed of consensus opinions of experts, case studies, or standards of care. RESULTS:The review finds the greatest level of evidence in support of the conservative management of pain through various classes of medications and topical treatments. Although injection-based interventions and neuromodulation approaches have been developed in the past few years, these techniques lack level A evidence from studies such as multiple randomized clinical trials or meta-analyses. The most invasive treatment discussed is surgical neurectomy, which also lacks level A evidence but has garnered support from retrospective reviews and prospective studies. LIMITATIONS:Attempts were made to gather studies from large databases. However, we acknowledge that our efforts do not cover all known publications on the management of ilioinguinal neuralgia. CONCLUSIONS:Based on the present literary review, the method of ilioinguinal neuralgia management with the strongest level of evidence in its favor is taking conservative measures, including topical and oral medications. The paper and accompanying original Table 2 provide a good summary of what current literature supports which treatment options.

In the United States, spinal cord injuries affect approximately 18,000 individuals annually, most commonly resulting from mechanical trauma. The consequent paraplegia severely impairs motor functions, creating an urgent need for innovative therapeutic strategies that extend beyond traditional rehabilitation and pharmacotherapy. This review assesses the effectiveness of Spinal Cord Stimulation (SCS) in improving motor function in patients with spinal cord injuries, with a particular focus on paraplegia. SCS, an emerging intervention, has gained attention for its ability to activate paralyzed muscles and enhance the effects of physical therapy. Our review demonstrates that SCS can lead to significant functional improvements when optimally combined with rehabilitation strategies. The success of SCS depends largely on the precise placement of electrodes with individualized parameters and the integration of stimulation with intensive physical training. This review underscores the considerable potential of SCS to improve motor outcomes in individuals with paraplegia caused by spinal cord injury, emphasizing the need for further research to optimize SCS parameters, electrode placement, and its integration with rehabilitation protocols. This review highlights the potential of SCS as a therapeutic intervention for improving motor function in individuals with paraplegia caused by spinal cord injuries.

BACKGROUND:Peripheral nerve stimulation (PNS) has been used for over 50 years to treat chronic pain. Since 2015, the Food and Drug Administration (FDA) has approved percutaneously implanted PNS leads and neurostimulators, offering a minimally invasive, non-opioid alternative for managing persistent and refractory chronic pain. OBJECTIVE:To evaluate the current evidence on PNS through a systematic review and meta-analysis. STUDY DESIGN:A systematic review and meta-analysis of randomized controlled trials (RCTs) on PNS for chronic pain management, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. METHODS:Quality was assessed using Cochrane review criteria for risk of bias and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials.A comprehensive literature search was conducted across multiple databases (1966-February 2025), supplemented by manual searches of bibliographies from relevant review articles. Included studies underwent quality assessment, best evidence synthesis, and grading using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Evidence levels were classified from Level I to Level V. OUTCOME MEASURES:The primary outcome was the proportion of patients achieving significant pain relief and functional improvement (>= 50%) sustained for at least 12 months. RESULTS:The present investigation identified 7 high-quality and 2 moderate-quality RCTs based on Cochrane criteria and 9 moderate-quality trials based on IPM-QRB criteria. Utilizing GRADE criteria, 7 of 9 studies demonstrated moderate evidence and clinical applicability, and 2 of 9 showed low evidence and applicability.Overall, the combined qualitative and quantitative analysis supported a fair (Level III) evidence level, with moderate certainty and moderate strength of recommendation for:Implantable PNS systems following a trial or selective lumbar medial branch stimulation without a trialTemporary PNS therapy for 60 days. LIMITATIONS:A key limitation remains the scarcity of high-quality studies. CONCLUSION:The evidence supports a fair (Level III) level of evidence with moderate certainty and recommendation strength, based on qualitative and quantitative analyses and GRADE assessment.

Cannabinoids have gained increasing attention as potential therapeutic agents in chronic pain management. Their mechanisms of action, mediated through CB1 and CB2 receptors, provide a pharmacological alternative to conventional analgesics. The evidence is strongest for neuropathic pain and multiple sclerosis-related spasticity, while the results for fibromyalgia, osteoarthritis, and musculoskeletal pain remain inconsistent. The average pain reduction is modest, often not exceeding 0.5–1.0 points on a 10-point scale, and therapeutic gains are offset by safety concerns. Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, while nabiximols (THC + CBD spray) are associated with dizziness in 25% of patients, somnolence in 8%, and treatment discontinuation in 12%. High-dose CBD also carries a measurable risk of hepatotoxicity. Regulatory heterogeneity further constrains trial feasibility, scalability, and patient access, with disparities evident across the United States, Europe, Canada, and Australia. Overall, cannabinoids provide modest, condition-specific analgesia and should be considered adjunctive rather than first-line options, reserved for patients unresponsive to conventional therapy. Future progress requires standardized formulations, harmonized international regulations, long-term safety data, and large-scale randomized controlled trials to clarify their role in evidence-based pain management.

BACKGROUND:Complex Regional Pain Syndrome (CRPS) is a challenging and often disabling condition marked by persistent pain, most commonly in a limb following injury or surgery. It presents with a wide array of symptoms, including intense pain, swelling, alterations in skin color and temperature, motor dysfunction, and trophic changes such as skin and tissue atrophy. While the precise cause of CRPS is not fully understood, it is thought to stem from abnormal nervous system activity, leading to heightened pain sensitivity and inflammatory responses. A thorough understanding of CRPS is essential for accurate diagnosis, effective treatment, and enhancing patients' quality of life.Although attempts have been made to distinguish between acute and chronic CRPS, there are currently no established diagnostic criteria specific to chronic CRPS in medical literature. OBJECTIVE:This ASIPP guidance document offers updated, evidence-based recommendations for the diagnosis and management of Chronic Complex Regional Pain Syndrome (CRPS), with a primary focus on introducing novel, time-based diagnostic criteria specific to the chronic phase. These proposed criteria address significant gaps in the current literature, where existing standards, such as the Budapest Criteria, do not sufficiently differentiate between the acute and chronic stages of the condition. METHODS:An expert panel convened by the American Society of Interventional Pain Physicians (ASIPP) conducted a comprehensive literature review and employed a structured consensus process to develop recommendations. Acknowledging that the clinical and pathological characteristics of CRPS change significantly beyond 12 months, the panel proposed chronic-specific diagnostic criteria based on disease duration, clinical history, physical examination findings, and optional diagnostic tests. These draft criteria were refined through multidisciplinary input and expert consensus. RESULTS:The diagnostic framework for chronic CRPS consists of four key components:General Criteria - Require fulfillment of the Budapest Criteria for at least 12 months, continued recognition of CRPS as a diagnosis of exclusion, and differentiation from generalized nociplastic pain syndromes.History-Based Criteria - Mandate the presence of at least three out of five specific historical features.Physical Examination Criteria - Include asymmetric limb findings, sensory disturbances, and musculoskeletal changes.Optional Diagnostic Testing - May involve assessments such as intraepidermal nerve fiber density (IENFD) and imaging evidence of regional bone demineralization.This framework builds upon the Budapest Criteria by incorporating time-dependent features of chronic CRPS, including musculoskeletal dystrophy, neurogenic inflammation, and sympathetic dysfunction. Emerging objective tools-such as quantitative sensory testing (QST), skin biopsy for IENFD, functional MRI, and serum biomarkers of neuroinflammation-may further support diagnosis in complex or uncertain cases.Treatment recommendations highlight a multimodal strategy that integrates physical rehabilitation, pharmacologic management of neuropathic pain, sympathetic nerve blocks, and advanced neuromodulation. Emphasis is placed on individualized care pathways tailored to disease stage and patient-specific characteristics. CONCLUSIONS:This article presents the first structured, time-sensitive diagnostic criteria for chronic CRPS, aimed at improving diagnostic accuracy and informing treatment strategies. Adoption of these criteria may enhance clinical outcomes and promote further research into the natural history and pathophysiology of CRPS progression.

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines.