Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

PURPOSE OF REVIEW: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. RECENT FINDINGS: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain.

Surgical Approaches in Total Hip Arthroplasty.

The Total Hip Arthroplasty (THA) has become one of the most reliable surgical interventions that has improved the quality of life in many patients. THA allows patients to have increased mobility, range of motion, and reduced pain in patients with degenerative hip joints. This surgical procedure has become an effective treatment option for several chronic conditions affecting the hip joint. Although this surgery has been shown to give promising results in patients with hip pathology, selecting the approach for THA is a critical step in pre-operative planning. The best approach for this surgical procedure depends on multiple factors and each present with their own challenges, success rates, and limitations. To further elucidate the advantages and disadvantages associated with different surgical approaches, we critically review each surgical approach along with the different causes of failure of the THA procedure.

Daridorexant for the Treatment of Insomnia.

Purpose of Review: Insomnia is a complex sleeping disorder that affects the lives of many individuals worldwide. Insomnia often occurs in the presence of coexisting comorbidities making it a complex disorder that requires a multifactorial approach to therapy. First-line therapy is cognitive-behavioral therapy for insomnia (CBT-I). Pharmacotherapy for insomnia falls into four classes based on mechanism of action: benzodiazepine receptor agonists (BZRAs), histamine receptor antagonists, melatonin receptor agonists, and dual orexin receptor antagonists (DORAs). Recent Findings: Daridorexant is a dual orexin type 1 and types 2 (OX1 and OX2) receptor antagonist that was recently approved by the US FDA for the treatment of adults suffering from insomnia. It was shown to be effective in reducing insomnia symptoms, increasing daytime functioning, and improving the overall quality of sleep. Daridorexant offers patients relief from insomnia while avoiding the severe side effects and dependency issues of traditional treatments like benzodiazepines and sedatives. Summary: In this article, we review the most recent data on insomnia treatments and summarize the safety and efficacy of daridorexant in treating insomnia.

Viloxazine for the Treatment of Attention Deficit Hyperactivity Disorder.

Purpose of Review: Attention deficit hyperactivity disorder (ADHD) is a widely diagnosed neurodevelopmental disorder giving rise to symptoms of hyperactivity, impulsivity, and inattentiveness that can impair daily functioning. Stimulants, such as methylphenidate and amphetamines, are the mainstay of treatment for ADHD. However, nonstimulant drugs such as viloxazine, atomoxetine, guanfacine, and clonidine are becoming more popular due to minimal adverse effects when compared to stimulants. Recent Findings: Viloxazine is a selective norepinephrine reuptake inhibitor (NRI) originally used to treat depression in adults with activity in both the noradrenergic as well as serotonergic pathways. Studies have demonstrated its efficacy for its use in the treatment of ADHD. Unlike stimulants, viloxazine has a decreased chance of substance abuse, drug dependance, and withdrawal symptoms upon the cessation of therapy. Additionally, dopamine levels in the nucleus accumbens after treatment with viloxazine are elevated considerably less in comparison with traditional stimulant ADHD treatments. Viloxazine provides an alternative, nonstimulant approach to treating ADHD. Summary: Viloxazine is a recently approved, non-stimulant medication functions by inhibiting the uptake of norepinephrine which has been seen to be decreased in patients with ADHD. When patients do not respond to first-line stimulants, cannot tolerate the side effects, or have contraindications to stimulants, viloxazine may be a nonstimulant option offering patients an increasing arsenal of medications to treat ADHD.

The role for high volume local infiltration analgesia with liposomal bupivacaine in total hip arthroplasty: A scoping review.

Introduction: Liposomal bupivacaine has been integrated into clinical practice within many surgical disciplines to reduce post-operative pain and opioid consumption. This novel agent has been utilized in this regard in many subdisciplines of orthopedic surgery. Total hip arthroplasty has significant opioid use post-operatively as compared to many other orthopedic disciplines. Objectives: The purpose of the present investigation is to summarize the current use of liposomal bupivacaine after total hip arthroplasty and to shed light on the prospect of liposomal bupivacaine to reduce opioid use after total hip arthroplasty. A tertiary purpose is to identify future areas of adjunctive pain measures that can assist in the reduction of opioid use after total hip arthroplasty. Methods: This IRB-exempt scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist strictly. The literature search was performed in Mendeley. Search fields were varied until redundant. All articles were screened by title and abstract and a preliminary decision to include an article was made. The full-text screening was performed on the selected articles. Any question regarding the inclusion of an article was discussed by three authors until an agreement was reached. Results: A total of 21 articles were included for qualitative description of the opioid epidemic, opioid overuse in total hip arthroplasty, and risk factors for opioid overuse in total hip arthroplasty. A total of 9 articles were included regarding the use of liposomal bupivacaine in total hip arthroplasty. Several risk factors have been identified for opioid overuse after total hip arthroplasty. These include younger age, an opioid risk tool score of > 7, a higher body mass index, chronic obstructive pulmonary disease, immunodeficiency syndromes, preexisting pain syndromes, peripheral vascular disease, anxiety and mood disorders, and substance abuse disorders. Liposomal bupivacaine reduces postoperative opioid use, patient-reported outcomes, length of stay, and time to ambulation, yet is more expensive than traditional bupivacaine. Conclusions: Liposomal bupivacaine represents a useful adjunct for multimodal pain strategies in total hip arthroplasty with sufficient evidence to suggest that it may be useful in decreasing postoperative opioid use. The high costs of LB represent a barrier to institutional acceptance of LB into standardized multimodal pain strategies. Further efforts should be aimed toward better understanding the current state of integration of LB into academic and private practice settings, industry movements to decrease the cost, and the role other adjunctive measures may have in reducing post-operative opioid use.

Activation of kappa opioid receptors in the dorsal raphe have sex dependent effects on social behavior in California mice.

Kappa opioid receptor activation has been linked to stress and anxiety behavior, thus leading to kappa antagonists being popularized in research as potential anxiolytics. However, while these findings may hold true in standard models, the neuromodulatory effects of social defeat may change the behavioral outcome of kappa opioid receptor activation. Previous research has shown that social defeat can lead to hyperactivity of serotonergic neurons in the dorsal raphe nucleus, and that inhibition of this increase blocks the social deficits caused by defeat. Kappa opioid receptor activation in the dorsal raphe nucleus works to decrease serotonergic activity. We injected the kappa opioid receptor U50,488 directly into the dorsal raphe nucleus of male and female, defeat and control adult California mice. Here we show evidence that U50,488 induces anxiety behavior in control male California mice, but helps relieve it in defeated males. Consistent with previous literature, we find little effect in females adding evidence that there are marked and important sex differences in the kappa opioid system.