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.

Efficacy of hyperbaric oxygen in patients with Crohn's disease: two case reports.

Crohn's disease is an inflammatory disease of the gastrointestinal tract, usually involving the ileum, that can lead to debilitating symptoms of abdominal pain, diarrhea and malabsorption during acute exacerbations. Because there is no known cause of the illness, treatment is based upon symptomatology and may ultimately require bowel resection if response to medical therapy is inadequate. Treatment with hyperbaric oxygen has shown promise in the reduction of inflammation associated with acute exacerbations of Crohn's disease, with alleviation of symptoms and an improvement in quality of life. We present two cases of pediatric patients with exacerbations of Crohn's disease who underwent cycles of hyperbaric oxygen therapy. Each patient was symptomatic and had no improvement despite prolonged medical therapy. Following treatment with hyperbaric oxygen, both patients showed resolution of the inflammatory lesions and improvement in conditions, allowing them to reduce drug therapy. Although the mechanisms by which hyperbaric oxygen reduce inflammation in Crohn's disease is poorly defined, this therapy seems to have offer a safe adjunct in the treatment of refractory exacerbations.

Therapeutic effect of hyperbaric oxygen on inclusion body myositis.

An inflammatory myopathy, inclusion body myositis (IBM) presents with progressive muscle weakness against a background of elevated creatine kinase and diffuse endomysial damage. Typically occurring in patients greater than 50 years of age, it is commonly misdiagnosed as polymyositis or other rheumatological disease and is often ineffectively treated with steroids [1]. The approach to IBM is frequently a clinical challenge due to its unique and often aberrant response to common treatment modalities. Here we report an apparent improvement in the clinical course of and associated laboratory findings in a patient with co-existing IBM following the use of hyperbaric oxygen therapy as an adjunct for managing ischemic colitis.

A comprehensive review of intraarticular knee injection therapy, geniculate injections, and peripheral nerve stimulation for knee pain in clinical practice.

The knee is the most common joint in adults associated with morbidity. Many pathologies are associated with knee damage, such as gout or rheumathoid arthritis, but the primary condition is osteoarthritis (OA). Not only can osteoarthritis cause significant pain, but it also can result in signficant disability as well. Treatment for this condition varies, starting off with oral analgesics and physical therapy to surgical total knee replacmenet. In the gamut of this various treatments, a conservative approach has included intra articular steroid injections. With time, researchers and clinicians determined that other components injected to the knee may additionally provide relief of this condition. In this investigation, we describe different types of knee injections such as platelet-rich plasma (PRP), hyaluronic acid, stem cells, and prolotherapy. Additionally, we describe the role of geniculate knee injections, radiofrequency, and periopheral nerve stimulation. These treatments should be considered for patients with knee pain refractory to conservative therapies.

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice.

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient's emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.

Comparing incidence of emergence delirium between sevoflurane and desflurane in children following routine otolaryngology procedures.

BACKGROUND: Emergence delirium (ED) is a state of aggressive agitation that can occur temporarily in the process of emerging from anesthesia in children exposed to volatile or intravenous anesthetics. Emergence delirium is typically assessed using the published and validated Pediatric Emergence Delirium (PAED) Scale. Due to some variation in properties between sevoflurane and desflurane for maintenance of anesthesia after standard sevoflurane induction, we designed a prospective study to examine potential differences in emergence behavior and incidence of ED in children undergoing elective ear-nose-throat surgery. METHODS: Forty-six children aged 12 months-7 years were randomly assigned to receive either sevoflurane (N.=23) or desflurane (N.=23) for maintenance of general anesthesia. All patients were extubated awake in the OR, and upon arrival in the PACU, PAED scores were assessed every 15 minutes until discharged. In addition to PAED scores, time to tracheal extubation, emergence behavior, pain scores, and recovery complications were recorded. RESULTS: We found no significant difference in incidence of ED or peak PAED scores between sevoflurane and desflurane groups (12 [0-18] versus 12 [0-20]; P=0.79). There were no significant differences between desflurane and sevoflurane with respect to incidence of adverse events, such as nausea, vomiting, laryngospasm, or excessive secretions. CONCLUSIONS: In conclusion, the use of desflurane for maintenance of anesthesia did not significantly affect the incidence or duration of ED when compared to sevoflurane. However, desflurane did not demonstrate any increase in adverse events, which may support its routine use in this patient population.

Mechanisms of hyperbaric oxygen and neuroprotection in stroke.

Cerebral vascular diseases, such as neonatal encephalopathy and focal or global cerebral ischemia, all result in reduction of blood flow to the affected regions, and cause hypoxia-ischemia, disorder of energy metabolism, activation of pathogenic cascades, and eventual cell death. Due to a narrow therapeutic window for neuroprotection, few effective therapies are available, and prognosis for patients with these neurological injuries remains poor. Hyperbaric oxygen (HBO) has been used as a primary or adjunctive therapy over the last 50 years with controversial results, both in experimental and clinical studies. In addition, the mechanisms of HBO on neuroprotection remain elusive. Early applications of HBO within a therapeutic window of 3-6h or delayed but repeated administration of HBO can either salvage injured neuronal tissues or promote neurobehavioral functional recovery. This review explores the discrepancies between experimental and clinical observations of HBO, focusing on its therapeutic window in brain injuries, and discusses the potential mechanisms of HBO neuroprotection.