Melatonin: Evolving Physiological Understanding and Potential Therapeutic Role in Pain Medicine Including Intervertebral Disc Degeneration.

BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, 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 receiving melatonin 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: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.

Posterior Sacroiliac Fusion Surgery: A Retrospective Single Center Study.

BACKGROUND: Chronic sacroiliitis has variable etiologies with numerous treatments of varying efficacy. In recent years, a novel posterior approach utilizing bone matrix has been developed although to date, there is limited data in the literature regarding efficacy and safety through this approach. Benefits described include reduced adverse outcomes and quicker recovery when compared to the lateral approach. OBJECTIVE: The present investigation focused on sacroiliac joint fusion through the posterior approach and outcomes including disability, pain, and use of analgesics post-surgery. STUDY DESIGN: This retrospective, single-center study was conducted evaluating safety and efficacy of sacroiliac fusion allograft implants (LinQ Implant System from PainTEQ; PsiF System from Omnia Medical). METHODS: A total of 72 posterior approach sacroiliac joint fusions were performed. Fifty-three individuals were enrolled and followed at LSU Health Shreveport as the sole investigational site between August 2020 and June 2024. Selected participant age ranged between 28 and 79 years, with a mean age of 53.4 years. The LinQ Implant System was the primary surgical hardware selected for implantation (83.0%), with the PsiF System chosen in the remaining cases. OUTCOME MEASURES: VAS Scores, disability changes, adverse outcomes, and analgesic use were compared after sacroiliac joint fusion via the posterior approach. RESULTS: Mean VAS Scores for SIJ Pain Intensity significantly decreased by 3.6 cm from a baseline score of 9.5 cm by the Specified End (June 1st, 2024). In this regard, 65.4% of patients experienced a 20% or greater improvement in pain, 38.5% of patients experienced a 50% or greater improvement in pain, and 26.9% of patients experienced a 70% or greater improvement in pain.  Zero (0) procedure-related adverse events nor intra- or post-operative complications occurred throughout the duration of the investigation. LIMITATIONS: Retrospective nature of the study without a control group. Fifty-four percent (39 of 72) completed minimum one year follow up. Further, the withdrawal rate was 26%. CONCLUSION: The results of the present investigation demonstrated effective outcomes with minimal adverse effects and improvements in disability over a three-year period in the largest single center study to date involving posterior approach sacroiliac joint fusion.

Percutaneous Coracohumeral Release for Patients with Adhesive Capsulitis: Two-Year Results from a Randomized Control Crossover Study.

BACKGROUND: Adhesive capsulitis (AC) causes a variety of symptoms, including but not limited to pain, stiffness, and a gradual restriction of active and passive range of motion (ROM). The coracohumeral ligament (CHL) plays an important role in this disease process, and percutaneous CHL release (PCHLR) has demonstrated efficacy in treating manifestations of this disorder that are refractory to pain medication, physical therapy, and local injections. Our previous study demonstrated one-year efficacy and durability, and this study examines 2-year data from our original randomized control crossover cohort. OBJECTIVE: To highlight the importance of extended follow-ups evaluating PCHLR's efficacy in AC management. STUDY DESIGN: A prospective, randomized, controlled, cross-over trial. SETTING: An academic medical center. METHODS: Patients with AC refractory to oral medication, physiotherapy, and at least one local injection were included in our original study. In all, there were initially 40 patients (46 shoulders), including 6 patients who underwent bilateral PCHLR using the Tenex® system. In this prospective study, 2 groups, the experiment group (scheduled to receive PCHLR) and the control group (scheduled to receive a local anesthetic in the coracohumeral ligament [LACHL]) were determined through 2-to-1 block randomization. Of these 46 shoulders initially treated, 39 remained in the study at one year. Twenty-six of the 39 shoulders were assigned to the PCHLR group whereas 13 were assigned to the LACHL group. Nine out of 13 shoulders in the LACHL group crossed over to the PCHLR group. Ultimately, 31 shoulders remained in the PCHLR group for 2-year analysis. The effectiveness of these interventions was assessed using a variety of parameters. Pain scores, ROM, and the Oxford Shoulder Score (OSS) were evaluated before the procedure and at one-year and 2-year follow-up visits. RESULTS: In this 2-year follow-up study, a total of 31 shoulders were sampled, comprising 22 women and 5 men, with 4 patients undergoing bilateral procedures. The mean age of the patients was 65 years (± 11.48). Patients' mean body mass index (BMI) was 36.33 (± 6.55), and the mean CHL thickness was 38.5 (± 3.45). Osteoarthritis was present in 11 cases. The mean follow-up period for the study was 29.7 months (± 6.39). The baseline mean external rotation was 30° (± 8), which increased to 62° (± 18) at one year and 53° (± 18) at 2 years. The baseline mean abduction was 60° (± 16), which improved to 77° (± 21) at one year and 68° (± 20) at 2 years. The median NRS decreased from 8 (IQR: 8, 9) at baseline to 3 (IQR: 2, 7) at one year and 5 (IQR: 2, 7) at 2 years. The baseline median OSS was 7 (IQR: 3, 10), which increased to 32 at one year and 22 (IQR: 15, 35) at 2 years. LIMITATIONS: The present investigation has a limited sample size of patients who have ROM impairment caused by CHL thickening. CONCLUSIONS: While the algorithm for AC care has seen little change for several decades, the authors suggest that PCHLR is a safe, durable, and effective option for cases of AC that are refractory to traditional management.

Trainee Insight into Pain Fellowship Programs: A Critical Evaluation of the Current Educational System by the APPD.

BACKGROUND: Since 1992, when the Accreditation Council of Graduate Medical Education (ACGME) acknowledged pain medicine as a subspecialty, the field has experienced significant growth in its number of programs, diversity of sponsoring specialties, treatment algorithms, and popularity among applicants. These shifts prompted changes to the educational model, overseen by program directors (PDs) and the ACGME. The pool of pain fellowship applicants also changed during that period. OBJECTIVES: This study aims to investigate trainees' reasons for applying to pain medicine fellowship programs as well as the applicants' specific expectations, interests, and motivations, thereby contributing to the remodeling and universal improvement of programs across the country. STUDY DESIGN: Online survey via SurveyMonkey. The online questionnaire targeted pain fellowship applicants in 2023 and current fellows in the US. METHODS: Our study was designed by board members of the Association of Pain Program Directors (APPD). The board disseminated a survey to those who applied to ACGME Pain Medicine fellowships in 2023 as well as to existing fellows. The survey was emailed to residency and fellowship PDs for dissemination to their trainees. The participants answered a 12-question survey on their reasons for pursuing pain medicine fellowships, expectations of and beyond those fellowships, and educational adjustments. RESULTS: There were 283 survey participants (80% applicants in residency training and 20% fellows). Participants ranked basic interventional procedures and a strong desire to learn advanced procedures as the most significant factors in pursuing a pain fellowship. Most trainees (70%) did not wish to pursue a 2-year fellowship, and 50% desired to go into private practice. LIMITATIONS: The relatively small number of respondents is a limitation that could introduce sampling error. Since most of the respondents were from the fields of physical medicine and rehabilitation (PM&R) and anesthesia, the use of convenience sampling reduced our ability to generalize the results to the wider community. Furthermore, approximately 80% of the trainees were residents, who might have had less experience in or knowledge of the survey's particulars than did the fellows. CONCLUSION: This survey demonstrated that procedural volume and diversity were important factors in trainees' decisions to apply to the field of pain medicine; however, extending the duration of a pain fellowship was not an option survey participants favored. Therefore, PDs and educational stakeholders in pain fellowship training need to develop creative strategies to maintain competitive applicants' interest while they adapt to our evolving field.

Perioperative Management of Antiplatelet and Anticoagulant Therapy in Patients Undergoing Interventional Techniques: 2024 Updated Guidelines from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The frequency of performance of interventional techniques in chronic pain patients receiving anticoagulant and antiplatelet therapy continues to increase. Understanding the importance of continuing chronic anticoagulant therapy, the need for interventional techniques, and determining the duration and discontinuation or temporary suspension of anticoagulation is crucial to avoiding devastating complications, primarily when neuraxial procedures are performed. Anticoagulants and antiplatelets target the clotting system, increasing the bleeding risk. However, discontinuation of anticoagulant or antiplatelet drugs exposes patients to thrombosis risk, which can lead to significant morbidity and mortality, especially in those with coronary artery or cerebrovascular disease. These guidelines summarize the current peer reviewed literature and develop consensus-based guidelines based on the best evidence synthesis for patients receiving anticoagulant and antiplatelet therapy during interventional procedures. STUDY DESIGN: Review of the literature and development of guidelines based on best evidence synthesis. OBJECTIVES: To provide a current and concise appraisal of the literature regarding the assessment of bleeding and thrombosis risk during interventional techniques for patients taking anticoagulant and/or antiplatelet medications. METHODS: Development of consensus guidelines based on best evidence synthesis included review of the literature on bleeding risks during interventional pain procedures, practice patterns, and perioperative management of anticoagulant and antiplatelet therapy. A multidisciplinary panel of experts developed methodology, risk stratification based on best evidence synthesis, and management of anticoagulant and antiplatelet therapy. It also included risk of cessation of anticoagulant and antiplatelet therapy based on a multitude of factors. Multiple data sources on bleeding risk, practice patterns, risk of thrombosis, and perioperative management of anticoagulant and antiplatelet therapy were identified. The relevant literature was identified through searches of multiple databases from 1966 through 2023. In the development of consensus statements and guidelines, we used a modified Delphi technique, which has been described to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approving specific guideline statements. Each panelist could suggest edits to the guideline statement wording and could suggest additional qualifying remarks or comments as to the implementation of the guideline in clinical practice to achieve consensus and for inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without primary conflict of interest. RESULTS: A total of 34 authors participated in the development of these guidelines. Of these, 29 participated in the voting process. A total of 20 recommendations were developed. Overall, 100% acceptance was obtained for 16 of 20 items. Total items were reduced to 18 with second and third round voting. The final results were 100% acceptance for 16 items (89%). There was disagreement for 2 statements (statements 6 and 7) and recommendations by 3 authors. These remaining 2 items had an acceptance of 94% and 89%. The disagreement and dissent were by Byron J. Schneider, MD, with recommendation that all transforaminals be classified into low risk, whereas Sanjeeva Gupta, MD, desired all transforaminals to be in intermediate risk. The second disagreement was related to Vivekanand A. Manocha, MD, recommending that cervical and thoracic transforaminal to be high risk procedures.Thus, with appropriate literature review, consensus-based statements were developed for the perioperative management of patients receiving anticoagulants and antiplatelets These included the following: estimation of the thromboembolic risk, estimation of bleeding risk, and determination of the timing of restarting of anticoagulant or antiplatelet therapy.Risk stratification was provided classifying the interventional techniques into three categories of low risk, moderate or intermediate risk, and high risk. Further, on multiple occasions in low risk and moderate or intermediate risk categories, recommendations were provided against cessation of anticoagulant or antiplatelet therapy. LIMITATIONS: The continued paucity of literature with discordant recommendations. CONCLUSION: Based on the review of available literature, published clinical guidelines, and recommendations, a multidisciplinary panel of experts presented guidelines in managing interventional techniques in patients on anticoagulant or antiplatelet therapy in the perioperative period. These guidelines provide a comprehensive assessment of classification of risk, appropriate recommendations, and recommendations based on the best available evidence.

Allopurinol: Clinical Considerations in the Development and Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Other Associated Drug Reactions.

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, requiring cessation of the medication with initial signs of rash or other early manifestations of SJS/TEN. One major consideration in the increased risk of allopurinol-mediated or modulated SJS/TEN is the need to have a lower dose in the setting of renal disease. The purpose of this review is not only to examine the involvement of allopurinol in SJS/TEN but also to provide detailed information about the drug, allopurinol, and general features and characteristics of SJS/TEN and other associated drug reactions.

The Evolving Role of Chlorthalidone and Hydrochlorothiazide as First-Line Treatments for Hypertensive Patients.

Hypertension is attributable long-term to various negative health outcomes, including atherosclerotic cardiovascular disease and, more broadly, to cardiovascular events such as congestive heart disease, myocardial infarction, heart failure, and stroke. Effective hypertension treatment is essential to lower the risk of these outcomes. Treatment of hypertension includes both nonpharmacologic and, if necessary, pharmacologic interventions. The drug classes proven in trials to decrease the risk of cardiovascular disease events in cases with hypertension include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. When considering thiazide diuretics as a first-line treatment, chlorthalidone (CTD) is currently recommended by the American College of Cardiology over hydrochlorothiazide (HCTZ). Previous studies have demonstrated that CTD is superior to HCTZ in preventing cardiovascular disease events. However, more recent studies have revealed that there is no significant difference in the results of patients treated with HCTZ versus those treated with CTD. Additionally, studies have revealed CTD has worse outcomes regarding side effects when compared to HCTZ. In this regard, it is essential to carefully consider which medication will best improve the outcomes of patients with hypertension while also causing few or easily manageable side effects.

Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such as chronic constipation and diarrhea. Both the extensive list of ASD-associated disorders and adverse effects from commonly prescribed medications for patients with ASD can impact presenting symptomatology. It is important to keep these potential interactions in mind when considering additional drug treatments or complementary therapies. This review addresses current literature involving novel pharmacological treatments such as oxytocin, bumetanide, acetylcholinesterase inhibitors, and memantine. It also discusses additional therapies such as diet intervention, acupuncture, music therapy, melatonin, and the use of technology to aid education. Notably, several of these therapies require more long-term research to determine efficacy in specific ASD groups within this patient population.

Treatment and Toxicity Considerations in Tuberculosis: A Narrative Review.

Tuberculosis remains one of the most significant bacterial infections plaguing the medical community worldwide. The bacteria Mycobacterium tuberculosis retains the ability to manifest as an active infection, latent infection, miliary infection, or reactivation of latent infections in times of immunosuppression. Therefore, the medication regimen to treat the condition revolves around four medications, each with a mechanism that targets a different part of the bacteria. Isoniazid weakens the cell wall but produces neuropathy and hepatotoxicity as side effects. Rifampin interrupts protein synthesis but creates the opportunity for many drug-to-drug interactions and red-orange discolorations as side effects. Pyrazinamide is poorly understood, but it is believed to acidify the internal environment of the bacteria, with gout exacerbations and arthralgias as major side effects. Ethambutol also works as a bacteriostatic medication to interrupt the cell membrane; however, its mechanism is poorly understood. The most concerning side effect is optic neuropathy. The unfavorable side effect profile for tuberculosis treatment may contribute to the higher rates of medication noncompliance with therapy and needs to be addressed in the future.

Ablation Compared to Pharmacological Treatment for the Reduction of Atrial Fibrillation Recurrence: A Meta-Analysis.

Atrial fibrillation (AF) is one of the most common heart arrhythmias, and due to its variable presentation, detecting and treating AF appropriately can reduce some of its serious complications. Among treatment options, surgical ablation and antiarrhythmic drug therapy are two of the most widely used choices. A systematic review and meta-analysis were conducted to examine the rates of AF recurrence in those treated with ablation compared to pharmacological treatment. Google Scholar and PubMed were searched for study trials published within the last decade that calculated the recurrence of AF symptoms in patient groups that received ablation or pharmacological treatment. Selected studies were analyzed in RevMan 5.4 software (The Cochrane Collaboration, London, England, UK), and each study's odds ratio and overall odds ratio were calculated using a 95% confidence interval. A total of seven studies with 2324 patients were analyzed for the meta-analysis, with 1162 patients receiving ablation and 1162 patients receiving pharmacological treatment. There was a statistically significant decrease in the recurrence of AF in the ablation group compared to the pharmacological treatment group, with a pooled odds ratio of 0.24 (CI 95% 0.14-0.39). AF treated with ablation was more effective in reducing AF recurrence than general pharmacological treatment.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

PURPOSE OF REVIEW: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments. This review analyzes data on efficacy, side effects, and safety of ITM and the pain control alternatives. RECENT FINDINGS: A comprehensive literature review was conducted to compare ITM with other analgesic techniques in post-cesarean patients. ITM was found to be as effective or better than other analgesic options, including bilateral quadratus lumborum block (QLB), opioid-free epidural analgesia (CSEA-EDA), and intravenous fentanyl. One study found that both ITM and oral analgesia were effective in pain control and that ITM caused fewer breakthrough pain events but had a longer duration and a greater rate of side effects than oral opioid analgesia. Commonly observed side effects of intrathecal opioids include nausea, vomiting, pruritus, and urinary retention, and it is thought that the adverse effects from intrathecal administration of opioids are short-lived. ITM may provide a decreased risk of DVT and coagulation by decreasing lower extremity weakness and numbness, thereby decreasing recovery time and increasing mobility. ITM is a safe and effective option for post-cesarean analgesia, with comparable pain relief to alternative forms of pain control, and side effects that are generally manageable. Further research is warranted to explore beneficial combinations with other methods of pain management and optimal dosing strategies.

Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review.

PURPOSE OF REVIEW: Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens. RECENT FINDINGS: However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

Rabies Vaccine for Prophylaxis and Treatment of Rabies: A Narrative Review.

Rabies, a millennia-old viral infection transmitted through animal bites, poses a lethal threat to humans, with a historic fatality rate of 100% if left untreated. Louis Pasteur's introduction of the rabies vaccine in 1885 marked a turning point in the battle against rabies, preventing numerous cases. The purpose of this paper is to review the historical development, current challenges, and future prospects of rabies vaccination and treatment, with emphasis on the importance of continued research and collaborative efforts in the quest to eradicate this deadly infection. Historical vaccine development progressed from inactivated to live-attenuated forms, with modern recombinant techniques showing promise. The preventive measures at present primarily involve vaccination, but challenges persist, such as differing safety profiles and immunogenicity among vaccine types. Pre-exposure prophylaxis with a three-dose vaccine series is crucial, especially in high-risk scenarios. Post-exposure prophylaxis combines human rabies immunoglobulin and inactivated rabies virus vaccine. The quest for the next generation of vaccines explores genetically modified and viral vector-based approaches; emerging treatments include gene therapy, virus-like particles, and monoclonal antibodies, offering hope for improved outcomes. Economic barriers to post-exposure prophylaxis, limited education, and awareness challenge rabies control. Cost-effective solutions and comprehensive awareness campaigns are vital for the successful eradication of rabies. More research and collaborative endeavors remain pivotal in the ongoing journey to eradicate rabies, one of the deadliest infectious diseases known to humans, if not met with prophylactic measures.

The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Diabetic Neuropathy: A Guide to Pain Management.

PURPOSE OF REVIEW: Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. RECENT FINDINGS: Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.

Evolving Concepts of Pain Management in Elderly Patients.

PURPOSE OF REVIEW: The elderly population typically suffer from a variety of diseases that mostly reflect the degenerative changes linked with the aging process. These diseases may be exacerbated by acute pain or by an abrupt aggravation of previously stable chronic pain. RECENT FINDINGS: Physical and psychological changes associated with aging may influence one's experience of pain and, as a result, the severity of pain. Pain treatment in the elderly can be complex and is often a budgetary burden on the nation's health care system. These difficulties arise, in part, because of unanticipated pharmacodynamics, changed pharmacokinetics, and polypharmacy interactions. Therefore, it is critical to integrate a multidisciplinary team to develop a management strategy that incorporates medical, psychological, and surgical methods to control persistent pain conditions. It is in this critical process that pain prediction models can be of great use. The purpose of pain prediction models for the elderly is the use of mathematical models to predict the occurrence and intensity of pain and pain-related conditions. These mathematical models employ a vast quantity of data to ascertain the many risk factors for the development of pain problems in the elderly, whether said risks are adjustable or not. These models will pave the way for more informed medical decision making that are based on the findings of thousands of patients who have previously experienced the same illness and related pain conditions. However, future additional research needs to be undertaken to build prediction models that are not constrained by substantial legal or methodological limitations.

An overview of the safety and efficacy of LX-9211 in treating neuropathic pain conditions.

INTRODUCTION: LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future. AREAS COVERED: This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed. EXPERT OPINION: In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

Analysis of Top 100 Articles Cited in Top Pain Journals: A Comprehensive Two Decade Bibliometric Analysis.

PURPOSE OF REVIEW: A bibliometric analysis was performed to analyze and compare the top 100 articles from the most well-known five pain journals: Pain, Pain Physician, Pain Medicine, Regional Anesthesia & Pain Medicine, and Journal of Pain. A query of the Scopus database was performed to filter the top 200 most cited articles from each journal. CY score was calculated for the top 200 articles from each journal by dividing the total number of citations by the number of years the article has been published. RECENT FINDINGS: All articles had a collective analysis of the top CY scores, the top 100 of which were further analyzed. The pain subtype, type of publication, country of origin, and senior author were extrapolated from these top 100 articles. Frequency tables were organized, revealing Pain Journal as the highest publishing journal out of the top 100 articles. Chronic pain was the most studied subtype of pain and narrative reviews were the most common type of evidence. Studies were also organized in five-year epochs to analyze the frequency of publications in these intervals. Results show that 2010-2014 had the highest frequency of articles published overall. Journal Impact Factor (JIF) is also an objective indicator of the average number of citations per published article from each journal. The journal with the highest JIF was Pain with an impact factor of 7.926. (6).