A randomized, placebo-controlled trial of long-acting dexamethasone viscous gel delivered by transforaminal injection for lumbosacral radicular pain.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03372161.

Substance P's Impact on Chronic Pain and Psychiatric Conditions-A Narrative Review.

Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress disorder (PTSD). Elevated SP levels are linked to heightened pain sensitivity and various psychiatric conditions, spurring interest in potential therapeutic interventions. In chronic pain, commonly associated with MDD and anxiety disorders, SP emerges as a key mediator in pain and emotional regulation. This review examines SP's impact on pain perception and its contributions to MDD, anxiety disorders, and PTSD. The association of SP with increased pain sensitivity and chronic pain conditions underscores its importance in pain modulation. Additionally, SP influences the pathophysiology of MDD, anxiety disorders, and PTSD, highlighting its potential as a therapeutic target. Understanding SP's diverse effects provides valuable insights into the mechanisms underlying these psychiatric disorders and their treatment. Further research is essential to explore SP modulation in psychiatric disorders and develop more effective treatment strategies.

The role of nitric oxide and hormone signaling in chronic stress, anxiety, depression and post-traumatic stress disorder.

This paper provides a summary of the role of nitric oxide (NO) and hormones in the development of chronic stress, anxiety, depression, and post-traumatic stress disorder (PTSD). These mental health conditions are prevalent globally and involve complex molecular interactions. Although there is a significant amount of research and therapeutic options available, the underlying mechanisms of these disorders are still not fully understood. The primary pathophysiologic processes involved in chronic stress, anxiety, depression, and PTSD include dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the intracellular influence of neuronal nitric oxide synthase (nNOS) on transcription factors, an inflammatory response with the formation of nitrergic oxidative species, and reduced serotonergic transmission in the dorsal raphe nucleus. Despite the extensive literature on this topic, there is a great need for further research to clarify the complexities inherent in these pathways, with the primary aim of improving psychiatric care.

The role of nitric oxide and neuroendocrine system in pain generation.

Previous studies have indicated a complex interplay between the nitric oxide (NO) pain signaling pathways and hormonal signaling pathways in the body. This article delineates the role of nitric oxide signaling in neuropathic and inflammatory pain generation and subsequently discusses how the neuroendocrine system is involved in pain generation. Hormonal systems including the hypothalamic-pituitary axis (HPA) generation of cortisol, the renin-angiotensin-aldosterone system, calcitonin, melatonin, and sex hormones could potentially contribute to the generation of nitric oxide involved in the sensation of pain. Further research is necessary to clarify this relationship and may reveal therapeutic targets involving NO signaling that alleviate neuropathic and inflammatory pain.

Pain Catastrophizing: How Far Have We Come.

The perception of pain is strongly influenced by various social, emotional, and cognitive factors. A psychological variable which has consistently been shown to exert its influence on pain is a cognitive process referred to as pain catastrophizing. Numerous studies have found it to be a strong predictor of pain intensity and disability across different clinical populations. It signifies a maladaptive response to pain marked by an exaggerated negative assessment, magnification of symptoms related to pain, and, in general, a tendency to experience marked pain-related worry, as well as experiencing feelings of helplessness when it comes to dealing with pain. Pain catastrophizing has been correlated to many adverse pain-related outcomes, including poor treatment response, unsatisfactory quality of life, and high disability related to both acute and chronic pain. Furthermore, there has been consistent evidence in support of a correlation between pain catastrophizing and mental health disorders, such as anxiety and depression. In this review, we aim to provide a comprehensive overview of the current state of knowledge regarding pain catastrophizing, with special emphasis on its clinical significance, and emerging treatment modalities which target it.

The Impact of Acute Postoperative Pain in Developing Chronic Pain after Total Knee Arthroplasty.

While total knee arthroplasties (TKAs) are performed with the intent to reduce pain, chronic postsurgical pain (CPSP) is one of the most well-documented complications that can occur following surgery. This study aimed to assess whether perioperative factors, focusing on acute postsurgical pain and perioperative opioid consumption, were associated with the development of chronic postsurgical pain. Under general anesthesia, 108 patients underwent TKA and were treated postoperatively with a multimodal analgesia approach. Numeric Rating Scale (NRS) pain scores at rest and with movement were recorded on postoperative days 0-3, 7, 14, and 30. Patients were sent a survey to assess chronic pain at months 22-66, which was examined as a single-group post hoc analysis. Based on the responses, patients were either classified into the CPSP or non-CPSP patient group. Chronic postsurgical pain was defined as an NRS score ≥ 4 with movement and the presence of resting pain. The primary outcome was a change in NRS. There were no differences in NRS pain scores with movement in the first 30 days postoperatively between patients with CPSP and without CPSP. Each unit increase in resting pain on postoperative days 3 and 14 was associated with significantly greater odds of CPSP presence (OR = 1.52; OR = 1.61, respectively), with a trend towards greater odds of CPSP at days 7 and 30 (OR = 1.33; OR = 1.43, respectively). We found that very intense pain in the initial phase seems to be related to the development of CPSP after TKA.

Systematic Review and Meta-Analysis of the Effectiveness of Radiofrequency Ablation of the Sacroiliac Joint.

PURPOSE OF REVIEW: To evaluate the effectiveness of radiofrequency neurotomy in managing sacroiliac joint pain utilizing a systematic review with meta-analysis of randomized controlled trials (RCTs) and observational studies. RECENT FINDINGS: The prevalence of sacroiliac joint pain is estimated at around 25% of low back pain cases, and its diagnosis lacks a gold standard. Treatments include exercise therapy, injections, ablation, and fusion, with variable effectiveness. COVID-19 altered utilization patterns of interventions, including sacroiliac joint procedures, and the evidence for these interventions remains inconclusive. Recently, Medicare has issued its local coverage determinations (LCDs) in the United States, which provides noncoverage of sacroiliac joint radiofrequency neurotomy. Additionally, a recent systematic review of sacroiliac joint injections showed Level III or fair evidence. The sacroiliac joint, a critical axial joint linking the spine and pelvis, contributes to low back pain. Its complex innervation pattern varies among individuals. Sacroiliac joint dysfunction, causing pain and stiffness, arises from diverse factors.The present systematic review and meta-analysis aimed to evaluate radiofrequency neurotomy's effectiveness for sacroiliac joint pain management by applying rigorous methodology, considering both RCTs and observational studies. Despite methodological disparities, the evidence from this review, supported by changes in pain scores and functional improvement, suggests Level III evidence with fair recommendation for radiofrequency neurotomy as a treatment option. The review's strengths include its comprehensive approach and quality assessment. However, limitations persist, including variations in criteria and technical factors, underscoring the need for further high-quality studies in real-world scenarios.

Effectiveness of Facet Joint Nerve Blocks in Managing Chronic Axial Spinal Pain of Facet Joint Origin: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic axial spinal pain is one of the major causes of disability. Literature shows that spending on low back and neck pain and musculoskeletal disorders continues to escalate, not only with disability, but also with increasing costs, accounting for the highest amount of various disease categories. Based on the current literature utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been shown as potential sources of spinal pain. Therapeutic facet joint interventional modalities of axial spinal pain include radiofrequency neurotomy, 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 facet joint nerve blocks 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) and observational studies utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. METHODS: The available literature on facet joint nerve blocks in axial spinal pain was reviewed. The quality assessment criteria utilized were the Cochrane review criteria to assess risk of bias, the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials, and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for nonrandomized studies. The evidence was graded according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment criteria. The level of evidence was 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 July 2023, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: This assessment identified 8 high-quality and one moderate quality RCTs and 8 high quality and 4 moderate quality non-randomized studies with application of spinal facet joint nerve blocks as therapeutic modalities. However, based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability, with 11 studies showing moderate levels of GRADE evidence and clinical applicability. LIMITATIONS: Despite the availability of multiple studies, the paucity of literature is considered as the major drawback. Based on Grading of Recommendations, Assessment Development, and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability. CONCLUSION: Based on the present systematic review and meta-analysis with 9 RCTs and 12 non-randomized studies, the evidence is Level II with moderate to strong recommendation for therapeutic facet joint nerve blocks in managing spinal facet joint pain.

The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders.

Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

Comprehensive, evidence-based, consensus guidelines for prescription of opioids for chronic non-cancer pain from the American Society of Interventional Pain Physicians (ASIPP)

Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed

Drug Safety and Suicidality Risk of Chronic Pain Medications.

Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led to an ever-increasing demand of pharmacological treatment and relief. This demand for medication, ranging from well-known groups, such as antidepressants and benzodiazepines, to more novel drugs, was followed by a rise in safety concerns of such treatment options. The validity, frequency, and diversity of such concerns are discussed in this paper, as well as their possible effect on future prescription practices. A specific caution is provided towards the psychological safety and toll of these medications, regarding suicidality and suicidal ideation. Most significantly, this paper highlights the importance of pharmacovigilance and underscores the necessity of surveillance programs when considering chronic pain medication.

Medial Branch Blocks and the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Thoracic Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Extensive research into potential sources of thoracic pain with or without referred pain into the chest wall has demonstrated that thoracic facet joints can be a potential source of pain confirmed by precise, diagnostic blocks.The objective of this systematic review and meta-analysis is to evaluate the effectiveness of medial branch blocks and radiofrequency neurotomy as a therapeutic thoracic facet joint intervention. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies of medial branch blocks and the radiofrequency neurotomy in managing thoracic pain utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases of RCTs and observational studies of medial branch blocks and radiofrequency neurotomy in managing chronic thoracic pain were identified from 1996 to December 2022 with inclusion of manual searches of the bibliography of known review articles and multiple databases. Methodologic quality and risk of bias assessment was also conducted. Evidence was synthesized utilizing principles of quality assessment and best evidence synthesis, with conventional and single meta-analysis. The primary outcome measure of success was 3 months of pain reduction for medial branch blocks and 6 months for radiofrequency thermoneurolysis for a single treatment. Short-term success was defined as up to 6 months and long-term was more than 6 months. RESULTS: This literature search yielded 11 studies meeting the inclusion criteria, of which 3 were RCTs and 8 were observational studies. Of the 3 RCTs, 2 of them assessed medial branch blocks and one trial assessed radiofrequency for thoracic pain. The evidence for managing thoracic pain with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 2 RCTs and 3 observational studies for medial branch blocks was Level II. For radiofrequency neurotomy, with the inclusion of one RCT of 20 patients in the treatment group and 5 observational studies, the evidence was Level III in managing thoracic pain. LIMITATIONS: There was a paucity of literature with RCTs and real-world pragmatic controlled trials. Even observational studies had small sample sizes providing inadequate clinically applicable results. In addition, there was heterogeneity of the available studies in terms of their inclusion and exclusion criteria, defining their endpoints and the effectiveness of the procedures. CONCLUSION: This systematic review and meta-analysis show Level II evidence of medial branch blocks and Level III evidence for radiofrequency neurotomy on a long-term basis in managing chronic thoracic pain. KEY WORDS: Chronic spinal pain, thoracic facet or zygapophysial joint pain, facet joint nerve blocks, medial branch blocks, controlled comparative local anesthetic blocks, diagnostic accuracy, radiofrequency neurotomy.

Systematic Review and Meta-Analysis of Effectiveness of Therapeutic Sacroiliac Joint Injections.

BACKGROUND: The sacroiliac joint is one of the proven causes of low back and lower extremity pain, ranging from 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis. Despite the difficulty of diagnosis, multiple therapeutic modalities including surgical and nonsurgical interventions have been utilized. Among the interventional modalities, intraarticular injections are commonly utilized. OBJECTIVE: To evaluate the therapeutic effectiveness of intraarticular injections in the sacroiliac joint. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies of the therapeutic effectiveness of intraarticular injections of the sacroiliac joint utilizing the Preferred Reporting Items For Systematic Reviews And Meta-Analyses (PRISMA) checklist. METHODS: The available literature on therapeutic sacroiliac joint intraarticular injections was reviewed. The quality assessment criteria utilized were the Cochrane review criteria to assess risk of bias, the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials, and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for nonrandomized studies. The level of evidence was based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data collection was performed including literature published from 1966 through December 2022, as well as manual searches of the bibliographies of known articles. OUTCOME MEASURES: Primary outcome measures include pain relief and improvement in functional status at 3 months for a single intervention. Only the studies performed under fluoroscopic guidance, with at least 3 months of follow-up were included. Duration of relief was categorized as short-term (< 6 months) and long-term (> 6 months). RESULTS: Based on the qualitative and quantitative analyses with a single-arm meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, and the inclusion of 11 RCTs (5 positive, 6 negative) and 3 observational studies (2 positive, one negative), the evidence was Level III or fair in managing low back pain of sacroiliac joint origin with sacroiliac joint injections. LIMITATIONS: This systematic review and meta-analysis are limited by lack of eligible studies, inconsistencies among the available studies, variations in techniques, variable diagnostic standards for inclusion criteria, and finally, the inability to correlate the results and perform an optimal systematic review and meta-analysis. CONCLUSION: The present systematic review and meta-analysis show an inability to perform conventional dual-arm analysis, whereas a single-arm meta-analysis demonstrated a difference of approximately 3 points on the Numeric Rating Scale (NRS) and 8 points on the Oswestry Disability Index (ODI). However, there were no studies that considered >= 50% relief as the criterion standard. Overall, the qualitative and quantitative evidence combined shows Level III or fair evidence for therapeutic sacroiliac joint injections for managing low back pain of sacroiliac joint origin. KEY WORDS: Chronic low back pain, sacroiliac joint pain, sacroiliac joint dysfunction, sacroiliitis, sacroiliac joint injection, sacroiliac joint nerve blocks, radiofrequency ablation, conventional radiofrequency, pulsed radiofrequency.

A Review of Recent Pharmacological Advances in the Management of Diabetes-Associated Peripheral Neuropathy.

Diabetic peripheral neuropathy is a common complication of longstanding diabetes mellitus. These neuropathies can present in various forms, and with the increasing prevalence of diabetes mellitus, a subsequent increase in peripheral neuropathy cases has been noted. Peripheral neuropathy has a significant societal and economic burden, with patients requiring concomitant medication and often experiencing a decline in their quality of life. There is currently a wide variety of pharmacological interventions, including serotonin norepinephrine reuptake inhibitors, gapentanoids, sodium channel blockers, and tricyclic antidepressants. These medications will be discussed, as well as their respective efficacies. Recent advances in the treatment of diabetes mellitus with incretin system-modulating drugs, specifically glucagon-like peptide-1 agonists, have been promising, and their potential implication in the treatment of peripheral diabetic neuropathy is discussed in this review.

Efficacy of Percutaneous Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Chronic refractory low back and lower extremity pain recalcitrant to conservative management and epidural injections secondary to postsurgery syndrome, spinal stenosis, and disc herniation are sometimes managed with percutaneous adhesiolysis. Consequently, this systematic review and meta-analysis was undertaken to assess the efficacy of percutaneous adhesiolysis in managing low back and lower extremity pain. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases from 1966 to July 2022, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included trials, meta-analysis, and best evidence synthesis was performed. The primary outcome measure was a significant reduction in pain (short term up to 6 months and long term more than 6 months). RESULTS: The search identified 26 publications, with 9 trials meeting the inclusion criteria. The results of dual-arm and single-arm analyses showed significant improvement in pain and function at 12 months. Opioid consumption was also significantly reduced at 6 months with dual-arm analysis, whereas single-arm analysis showed a significant decrease from baseline to treatment at the 3-, 6-, and 12-month analyses. At 1 year follow-up, seven of seven trials were positive for improvements in pain relief, function, and diminution of opioid use. DISCUSSION: Based on the present systematic review of nine RCTs, the evidence level is I to II, with moderate to strong recommendation for percutaneous adhesiolysis in managing low back and lower extremity pain. The limitations of the evidence include paucity of literature, lack of placebo-controlled trials, and the majority of the trials studying post lumbar surgery syndrome. CONCLUSION: The evidence is level I to II or strong to moderate based on five high-quality and two moderate-quality RCTs, with 1 year follow-up that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain.

Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain.

Chronic pain is a pressing medical and socioeconomic issue worldwide. It is debilitating for individual patients and places a major burden on society in the forms of direct medical costs and lost work productivity. Various biochemical pathways have been explored to explain the pathophysiology of chronic pain in order to identify biomarkers that can potentially serve as both evaluators of and guides for therapeutic effectiveness. The kynurenine pathway has recently been a source of interest due to its suspected role in the development and sustainment of chronic pain conditions. The kynurenine pathway is the primary pathway responsible for the metabolization of tryptophan and generates nicotinamide adenine dinucleotide (NAD+), in addition to the metabolites kynurenine (KYN), kynurenic acid (KA), and quinolinic acid (QA). Dysregulation of this pathway and changes in the ratios of these metabolites have been associated with numerous neurotoxic and inflammatory states, many of which present simultaneously with chronic pain symptoms. While further studies utilizing biomarkers to elucidate the kynurenine pathway's role in chronic pain are needed, the metabolites and receptors involved in its processes nevertheless present researchers with promising sources of novel and personalized disease-modifying treatments.

Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions.

The pathogenesis of chronic pain entails a series of complex interactions among the nervous, immune, and endocrine systems. Defined as pain lasting or recurring for more than 3 months, chronic pain is becoming increasingly more prevalent among the US adult population. Pro-inflammatory cytokines from persistent low-grade inflammation not only contribute to the development of chronic pain conditions, but also regulate various aspects of the tryptophan metabolism, especially that of the kynurenine pathway (KP). An elevated level of pro-inflammatory cytokines exerts similar regulatory effects on the hypothalamic-pituitary-adrenal (HPA) axis, an intricate system of neuro-endocrine-immune pathways and a major mechanism of the stress response. As the HPA axis counters inflammation through the secretion of endogenous cortisol, we review the role of cortisol along with that of exogenous glucocorticoids in patients with chronic pain conditions. Considering that different metabolites produced along the KP exhibit neuroprotective, neurotoxic, and pronociceptive properties, we also summarize evidence rendering them as reliable biomarkers in this patient population. While more in vivo studies are needed, we conclude that the interaction between glucocorticoid hormones and the KP poses an attractive venue of diagnostic and therapeutic potential in patients with chronic pain.

The Discrepancy and Agreement between Patient-Reported Percentage Pain Reduction and Calculated Percentage Pain Reduction in Chronic Pain Patients.

Two derivatives of the numeric rating scale (NRS) and visual analog scale (VAS), namely patient-reported percentage pain reduction (PRPPR) and calculated percentage pain reduction (CPPR), are commonly used when evaluating pain reduction. A small number of studies have attempted to assess the agreement between PRPPR and CPPR. However, they have been limited in their scope by a focus on specific types of pain, or by their focus on specific treatment modalities. As far as the authors of this article are aware, this is the first study to assess the agreement between PRPPR and CPPR in chronic pain patients, as well as the first to assess how the duration of treatment affects the correlations between PRPPR and CPPR. The aim of this retrospective analysis was to determine whether the duration of treatment affects CPPR and PRPPR, and the discrepancy and agreement between the two. Additionally, the study assessed whether individual treatment modalities, or the lack there of, impacted the discrepancy and correlation between PRPPR and CPPR. The mean PRPPR and CPPR for the entire patient population were 59.98 and 40.71, respectively. The mean discrepancy between the two parameters was 19.27. The agreement between PRPPR and CPPR, as measured by the concordance correlation coefficient, was 0.984 (95% C.I., 0.982-0.986).