An extract of phase II and III trials on recent developments in managing neuropathic pain syndromes: diabetic peripheral neuropathy, trigeminal neuralgia, and postherpetic neuralgia.

INTRODUCTION: Neuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP. AREAS COVERED: In this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov. EXPERT OPINION: All the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis.

BACKGROUND: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG). METHODS: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed. RESULTS: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP. CONCLUSION: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.

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.

Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

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).

Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons.

PURPOSE OF REVIEW: Osteoarthritis (OA) is a prevalent and debilitating condition characterized by joint degeneration and pain. Current treatment options aim to alleviate symptoms and slow disease progression but lack curative potential. Stem cell therapies have emerged as a promising alternative. This article explores the epidemiology, pathophysiology, clinical manifestations of hip and knee OA, and the evolving role of stem cell therapies in their treatment. RECENT FINDINGS: The global prevalence of OA, with knee OA being the most common form, has fueled the demand for stem cell therapies. Despite limited robust evidence supporting their efficacy, clinical trials investigating stem-cell treatments for OA have reported encouraging radiological and clinical improvements. Stem cell therapies offer potential disease-modifying benefits through immunomodulatory actions, growth factor secretion, and chondrogenic capabilities. Adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in clinical trials for OA treatment, offering potential pain relief and functional improvement. ADMSCs possess advantages such as accessibility and a favorable safety profile, making them a viable option for OA management. Although other stem-cell types, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have been used in OA treatment, ADMSCs have demonstrated superior outcomes. By providing a comprehensive overview of the evolving landscape of stem cell therapies for hip and knee OA, this article highlights the potential of stem-cell treatments to address the limitations of current therapies. However, further research is required to establish their long-term efficacy, identify optimal stem-cell types, and develop standardized protocols.

Effectiveness of Virtual Reality-Based Rehabilitation Interventions in Improving Postoperative Outcomes for Orthopedic Surgery Patients.

PURPOSE OF REVIEW: The surge in orthopedic surgeries strains the US healthcare system, necessitating innovative rehabilitation solutions. This review examines the potential of virtual reality (VR)-based interventions for orthopedic rehabilitation. RECENT FINDINGS: The effectiveness of VR-based interventions in orthopedic surgery patients is scrutinized. While some studies suggest better patient-reported outcomes and satisfaction, mixed results emerge from others, demonstrating comparable or varied results compared to traditional rehabilitation. The underlying mechanisms of VR-based rehabilitation are elucidated, showing its positive impact on proprioception, pain management, agency, and balance. Challenges of unfamiliarity, patient engagement, and drop-out rates are identified, emphasizing the need for tailored approaches. VR technology's immersive environments and multisensory experiences offer a novel approach to addressing functional deficits and pain post-surgery. The conclusion drawn is that VR-based rehabilitation complements rather than replaces conventional methods, potentially aiding in pain reduction and functional improvement. VR-based rehabilitation holds promise for enhancing orthopedic surgery outcomes, presenting a dynamic approach to recovery. Its potential to reshape healthcare delivery and reimbursement structures underscores its significance in modern healthcare. Overall, VR-based rehabilitation offers a promising avenue for optimizing postoperative recovery in orthopedic surgery patients.

Emerging Medications and Strategies in Acute Pain Management: Evolving Role of Novel Sodium and Calcium Channel Blockers, Peptide-Based Pharmacologic Drugs, and Non-Medicinal Methods.

PURPOSE OF REVIEW: The present investigation evaluated integration of novel medication technology to enhance treatment options, while improving patient outcomes in acute pain management. In this regard, we focused on determining the role of development and utilization of cutting-edge pharmaceutical advancements, such as targeted drug delivery systems, as well as non-pharmacologic interventions in addressing acute pain states. Further research in this area is warranted related to the need for increased patient comfort and reduced adverse effects. RECENT FINDINGS: Recent innovations and techniques are discussed including pharmacologic drugs targeting sodium and calcium channels, peptide-based pharmacologic drugs, and non-medicinal methods of alleviating pain such as soothing music or virtual reality. The present investigation included review of current literature on the application of these innovative technologies, analyzing mechanisms of action, pharmacokinetics, and clinical effectiveness. Our study also investigated the potential benefits in terms of pain relief, reduced side effects, and improved patient adherence. The research critically examines the challenges and considerations associated with implementing these technologies in acute pain management, considering factors like cost, accessibility, and regulatory aspects. Additionally, case studies and clinical trials are highlighted which demonstrate practical implications of these novel medication technologies in real-world scenarios. The findings aim to provide healthcare professionals with a comprehensive understanding of the evolving landscape in acute pain management while guiding future research and clinical practices toward optimizing their use in enhancing patient care.

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.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

The Role of Platelet Rich Plasma in Vertebrogenic and Discogenic Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

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.

Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

PURPOSE OF REVIEW: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges. RECENT FINDINGS: Low SES presents barriers to effective pain care, while gender differences and the prevalence of chronic pain in aging adults emphasize the need for tailored approaches. The association between chronic pain and physical comorbidities like cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus reveals shared risk factors and further highlights the importance of integrated treatment strategies. Chronic pain and mental health are intricately linked through biochemical mechanisms, profoundly affecting overall quality of life. This review explores pharmacologic treatment for chronic pain, particularly opioid analgesia, with attention to the risk of substance misuse and the ongoing opioid epidemic. We discuss the potential role of medical cannabis as an alternative treatment with a nuanced perspective on its impact on opioid use. Addressing the totality and complexity of pain states is crucial to individualizing chronic pain management. With different types of pain having different underlying mechanisms, considerations should be made when approaching their treatment. Moreover, the synergistic relationship that pain states can have with other comorbidities further complicates chronic pain conditions.

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.

Efficacy and Safety of Ketamine-Dexmedetomidine Versus Ketamine-Propofol Combination for Periprocedural Sedation: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: The combination of ketamine with propofol and dexmedetomidine has gained popularity for sedation and general anesthesia in different populations. In our meta-nalysis, we helped the anesthesiologists to know the efficiency and the efficacy of both combinations in adult and pediatric patients. METHODS: We searched PubMed, CENTRAL, Web of Science, and Scopus from inception to August 1, 2023. Our outcome parameters for efficacy were recovery time, pain score, and physician satisfaction while for safety were the related cardiorespiratory, neurological, and gastrointestinal adverse events. RECENT FINDINGS: Twenty-two trials were included with a total of 1429 patients. We found a significantly longer recovery time in the ketadex group of 7.59 min (95% CI, 4.92, 10.26; I2 = 94%) and a significantly less pain score of - 0.72 (95% CI, - 1.10, - 0.34; I2 = 0%). Adults had a significantly better physician satisfaction score with the ketofol group, odds ratio of 0.29 (95% CI, 0.12, 0.71; I2 = 0%). Recovery agitations were higher in the ketofol group with an odds ratio of 0.48 (95% CI, 0.24, 0.98; I2 = 36%). Furthermore, we found a significant difference between the combinations with a higher incidence in the ketadex group with pooled odds ratio of 1.75 (95% CI, 1.06, 2.88; I2 = 15%). Ketadex was associated with lower pain scores, hypoxic events and airway obstruction, and emergence agitation. At the same time, ketofol had much more clinician satisfaction which might be attributed to the shorter recovery time and lower incidence of nausea and vomiting. Therefore, we suppose that ketadex is the better combination in periprocedural sedation for both adult and pediatric patients who are not at greater risk for postoperative nausea and vomiting.

Peripheral Nerve Stimulation in Postoperative Analgesia: A Narrative Review.

PURPOSE OF REVIEW: Recent research has shown the effectiveness of peripheral nerve stimulators (PNS) in managing chronic pain conditions. Ongoing studies aim to explore its potential application in treating acute postoperative pain states. The purpose of this systematic review is to assess the role of PNS in providing relief for postoperative pain. RECENT FINDINGS: Clinical studies investigating the use of peripheral nerve stimulators (PNS) for analgesia following various surgeries, such as total knee arthroplasty, anterior cruciate ligament repair, ankle arthroplasty, rotator cuff repair, hallux valgus correction, and extremity amputation, have shown promising results. Lead placement locations include the brachial plexus, sciatic, femoral, tibial, genicular, perineal, sural, radial, median, and ulnar nerves. These studies consistently report clinically significant reductions in pain scores, and some even indicate a decrease in opioid consumption following PNS for postoperative pain. PNS involves the subcutaneous placement of electrode leads to target peripheral nerve(s) followed by delivery of an electric current via an external pulse generator. While the precise mechanism is not fully understood, the theory posits that PNS modulates electrical stimulation, hindering the signaling of nociceptive pain. PNS presents itself as an alternative to opioid therapy, holding promise to address the opioid epidemic by offering a nonpharmacologic approach for both acute and chronic pain states.

IPACK Block Efficacy for Acute Pain Management after Total Knee Replacement: A Review.

PURPOSE OF REVIEW: Patients often experience a significant degree of knee pain following total knee replacement (TKR). To alleviate this pain, nerve blocks may be performed such as the adductor canal block (ACB). However, ACBs are unable to relieve pain originating from the posterior region of the knee. A new type of nerve block known as the IPACK block may be used in conjunction with ACBs as it is designed to inhibit nerve branches innervating this area. In this article, we examine the rationale behind the IPACK procedure, how it is performed, and clinical trials examining its efficacy. RECENT FINDINGS: 5 of the 7 clinical trials examined in this article showed the IPACK + ACB block to show superior efficacy in treating pain following TKR compared to other blocks. These blocks included PMDI+ACB, SPANK+ACB, PAI+ACB, ACB alone, and SCAB. 2 of the 7 clinical trials showed the IPACK + ACB to be less effective in managing patients pain following TKR compared to other blocks which included the CACB and 4 in 1 block. In most instances, the IPACK + ACB showed superior efficacy in managing patients' pain following TKR when compared to other types of nerve blocks. This was determined by measuring usage of opioids, reported postoperative pain, and length of hospital stays following TKR. Thus, we suppose the IPACK block may be used in conjunction with the ACB to effectively reduce patient's pain following TKR.

Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.