A Comprehensive Review and Update of Post-surgical Cutaneous Nerve Entrapment.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding post-surgical cutaneous nerve entrapment, epidemiology, pathophysiology, and clinical presentation. It focuses mainly on nerve entrapment leading to chronic pain and the available therapies. RECENT FINDINGS: Cutaneous nerve entrapment is not an uncommon result (up to 30% of patients) of surgery and could lead to significant, difficult to treat chronic pain. Untreated, entrapment can lead to neuropathy and damage to enervated structures and musculature, and significant morbidity and financial loss. Nerve entrapment is defined as pressure neuropathy from chronic compression. It causes changes to all layers of the nerve tissue. It is most significantly associated with hernia repair and other procedures employing a Pfannenstiel incision. The initial insult is usually incising of the nerve, followed by formation of a neuroma, incorporation of the nerve during closing, or constriction from adhesions. The three most commonly involved nerves are the iliohypogastric, ilioinguinal, and genitofemoral nerves. Cutaneous abdominal nerve entrapment could occur during thoracoabdominal surgery. The presentation of nerve entrapment usually involved post-surgical pain in the territory innervated by the trapped nerve, possibly with radiation that tracks the nerve course. Once a suspected neuropathy is identified, it can be diagnosed with relief in pain after a nerve block has been instilled. Treatment is usually started with pharmaceutical solutions, topical first and oral if those fail. Most patients require escalation to a second line of treatment and see good result with injection therapy. Those that require further escalation can choose between ablation and surgical therapies. Post-surgical nerve entrapment is not uncommon and causes serious morbidity and financial loss. It is underdiagnosed and thus undertreated. Preventing nerve entrapment is the best treatment; when it does occur, options include topical and oral analgesics, nerve blocks, ablation therapy, and repeat surgery.

Diagnosis, Treatment, and Management of Dejerine-Roussy Syndrome: a Comprehensive Review.

PURPOSE OF REVIEW: Post-stroke pain represents a complex condition with few standardized diagnostic criteria. As such, the array of symptoms is often difficult to categorize and diagnose. Central post-stroke pain (CPSP), also known as Dejerine-Roussy syndrome, presents as painful paresthesia in any part of the body that is usually coupled with sensory abnormalities. RECENT FINDINGS: In patients who had experienced a cerebrovascular accident, CPSP typically affects the same areas of the body that are also impacted by the general motor and sensory deficits that result from stroke. Though it is generally debated, CPSP is thought to result from a lesion in any part of the central nervous system. Pain usually presents in the range of 3-6 months after the occurrence of stroke, manifesting contralaterally to the lesion, and most commonly involving the upper extremities. For the most accurate diagnosis of CPSP, a thorough history and clinical examination should be supplemented with imaging. Infarcted areas of the brain can be visualized using either CT or MRI. First-line treatment of CPSP is pharmacologic and consists of a three-drug regimen. Despite this, CPSP is often refractory to medical management producing only modest pain reduction in a limited subset of patients. Adverse effects associated with pharmacologic management of CPSP and frequent recalcitrance to treatment have driven alternative minimally invasive methods of pain control which include transcranial stimulation, deep brain stimulation, and neuromodulation. The aim of this review is to provide a comprehensive update to recent advances in the understanding of the treatment and management of CPSP.

Expanding Role of the Erector Spinae Plane Block for Postoperative and Chronic Pain Management.

PURPOSE OF REVIEW: The erector spinae plane block (ESPB), first described in 2016, offers the promise of becoming a safe, less invasive, and technically less demanding alternative to conventional thoracic regional anesthetic techniques including thoracic epidurals and traditional paravertebral blocks. Clinical and cadaveric studies suggest that ESPB acts on the ventral rami of spinal nerves in the paravertebral space via penetration of the intertransverse connection tissues and moreover achieves visceral analgesia via the rami communicantes and sympathetic chain. RECENT FINDINGS: The block has garnered considerable appeal related to an inherently lower risk of neurovascular and pleural injury, low risk of local anesthetic systemic toxicity, and relative technical simplicity in comparison with epidural or paravertebral blockade. It has been utilized in the treatment of acute perioperative pain in a variety of clinical applications including breast, thoracic, and abdominal surgeries and trauma and may even offer some benefit in spine surgery. Given the combination of its efficacy and decreased associated risk when performed for perioperative pain, use of ESPB should be further explored for the management of chronic pain. Current literature at this time is limited to case studies and series performed by select groups. Though it is important to consider ESPB for chronic pain, further studies are needed to evaluate the efficacy and safety of the ESPB in the management of both acute and chronic pain.

Recent Advances in the Understanding and Management of Carpal Tunnel Syndrome: a Comprehensive Review.

PURPOSE OF REVIEW: Carpal tunnel syndrome (CTS) is an entrapment neuropathy that involves the compression of the median nerve at the wrist and is considered the most common of all focal entrapment mononeuropathies. CTS makes up 90% of all entrapment neuropathies diagnosed in the USA and affects millions of Americans. RECENT FINDINGS: Age and gender likely play a role in the development of CTS, but additional studies may further elucidate these associations. Of known associated risk factors, diabetes mellitus seems to have the greatest association with CTS. One of the most commonly reported symptoms in CTS is a "pins-and-needles" sensation in the first three fingers and nocturnal burning pain that is relieved with activity upon waking. Treatment for CTS is variable depending on the severity of symptoms. Conservative management of CTS is usually considered first-line therapy. In cases of severe sensory or motor deficit, injection therapy or ultimately surgery may then be considered. Still CTS is often difficult to treat and may be reoccurring. Novel treatment modalities such as laser and shockwave therapy have demonstrated variable efficacy though further studies are needed to assess for safety and effect. Given the unknown and potentially complex etiology of CTS, further studies are needed to explore combinations of diagnostic and therapeutic modalities.

The Utilization of Mu-Opioid Receptor Biased Agonists: Oliceridine, an Opioid Analgesic with Reduced Adverse Effects.

PURPOSE OF REVIEW: The purpose of this review is to summarize the current understanding of opioid pathways in mediating and/or modulating analgesia and adverse effects. Oliceridine is highlighted as a novel mu-opioid receptor agonist with selective activation of G protein and ß-arrestin signaling pathways. RECENT FINDINGS: Oliceridine (TRV130; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine) is a novel MOR agonist that selectively activates G protein and ß-arrestin signaling pathways. A growing body of evidence suggests that compared to existing MOR agonists, Oliceridine and other G protein-selective modulators may produce therapeutic analgesic effects with reduced adverse effects. Oliceridine provides analgesic benefits of a pure opioid agonist while limiting related adverse effects mediated through the ß-arrestin pathway. Recent insights into the function and structure of G protein-coupled receptors has led to the development of novel analgesic therapies.

CGRP Antagonists for the Treatment of Chronic Migraines: a Comprehensive Review.

PURPOSE OF REVIEW: The purpose of the following review is to summarize the most recent understanding of migraine pathophysiology, as well as of basic and clinical science pharmacologic literature regarding the development of calcitonin gene receptor peptide (CGRP) antagonists as a novel therapeutic modality for the treatment of migraine headaches. A review is provided of erenumab, the first of its class FDA approved CGRP antagonist. RECENT FINDINGS: Despite its high prevalence, the occurrence and treatment of migraine headaches is poorly understood. Erenumab and CGRP antagonists as a whole significantly reduce the average number of migraine days experienced in migraine sufferers. CGRP antagonists appear to significantly improve treatment outcomes in patients who suffer from episodic and chronic migraines. Erenumab is the first CGRP antagonist to be FDA approved for public use; however, further development of biologics in this class is underway.

Predictors of colorectal carcinoma and inflammatory bowel disease in patients with colonic wall thickening.

Background and Aim: Colonic wall thickening (CWT) is commonly associated with clinically significant pathologies, but predictive factors of such pathologies are not well known. This study aims to identify the predictors of clinically significant pathologies, such as colorectal carcinoma (CRC) and inflammatory bowel disease (IBD), in patients with CWT. Methods: Subjects with an abnormal abdominal computed tomography (CT) and a follow-up colonoscopy between 2010 and 2020 were retrospectively reviewed. Patients with CWT in the CT were included and examined in this study. A multivariable logistic regression analysis was performed to assess for factors independently associated with CRC or IBD in these subjects. Receiver operating characteristic (ROC) curve analysis was used to further examine significant parameters in multivariable logistic regression analysis. Results: Among 403 patients with CWT on CT scans who underwent a colonoscopy, 269 subjects who met the inclusion criteria were identified and studied. On multivariable logistic regression models, elevated platelet count, low hematocrit, and localized CWT were found to be independently associated with CRC, while elevated platelet count and younger age were independently associated with IBD. On ROC curve analysis for CRC, area under the curve (AUC) for hematocrit, platelets, and localized CWT was 0.76, 0.75, and 0.61, respectively. On ROC curve analysis for IBD, AUC for age and platelets was 0.90 and 0.69, respectively. Conclusion: Elevated platelet count, low hematocrit, and localized CWT can be potentially used as predictors of CRC in patients with CWT. Elevated platelet count and young age can be used to predict IBD in these patients.

Supply, Demand, and Quality: A Three-Pronged Approach to Blood Product Management in Developing Countries.

While transfusion of blood and blood products is instinctively linked to the provision of emergent care, blood and blood products are also routinely used for the treatment of subacute and chronic conditions. Despite the efforts of the World Health Organization and others, developing countries are faced with a three-part problem when it comes to access to and delivery of transfusions: insufficient supply, excessive demand, and inadequate quality of available supply. Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. While increased awareness of HIV and improved testing techniques have jointly reduced infection-related apprehensions and improved the quality of available blood and blood products, continued efforts are warranted to bolster testing for other bloodborne pathogens. Similarly, although prevalence rates of anemia are high in some areas of the world, success in adequate widespread management of these conditions has been limited. One of the keys to expanding access to high-quality blood and blood products is thus to improve medical management of conditions that would otherwise require transfusion. Through a three-pronged approach to address quantity, quality, and demand, developing countries can enable themselves to build toward self-sufficient blood management services and increased independence from the support of international organizations.

Factors associated with reduced infliximab exposure in the treatment of pediatric autoimmune disorders: a cross-sectional prospective convenience sampling study.

BACKGROUND: Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy. METHODS: In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient demographic and clinical data were collected by chart review and evaluated for their relationship with IFX clearance. RESULTS: IFX trough concentrations ranged from 0 to > 40 µg/mL and were 3-fold lower in children with IBD compared to children with JIA (p = 0.0002) or uveitis (p = 0.001). Children with IBD were found to receive lower IFX doses with longer dosing intervals, resulting in dose intensities (mg/kg/day) that were 2-fold lower compared to children with JIA (p = 0.0002) or uveitis (p = 0.02). Use of population pharmacokinetic analysis to normalize for variation in dosing practices demonstrated that increased IFX clearance was associated with ADA positivity (p = 0.004), male gender (p = 0.02), elevated erythrocyte sedimentation rate (ESR) (p = 0.02), elevated c-reactive protein (CRP) (p = 0.001), reduced serum albumin concentrations (p = 0.0005), and increased disease activity in JIA (p = 0.009) and IBD (p ≤ 0.08). No significant relationship between diagnosis and underlying differences in IFX clearance was observed. Multivariable analysis by covariate population pharmacokinetic modeling confirmed increased IFX clearance to be associated with anti-IFX antibody positivity, increased ESR, and reduced serum albumin concentrations. CONCLUSIONS: Enhanced IFX clearance is associated with immunogenicity and inflammatory burden across autoimmune disorders. Higher systemic IFX exposures observed in children with rheumatologic disorders are driven primarily by provider drug dose and interval selection, rather than differences in IFX pharmacokinetics across diagnoses. Despite maintenance IFX dosing at or above the standard recommended range for IBD (i.e., 5 mg/kg every 8 weeks), the dosing intensity used in the treatment of IBD is notably lower than dosing intensities used to treat JIA and uveitis, and may place some children with IBD at risk for suboptimal maintenance IFX exposures necessary for treatment response.

Dorsal Root Ganglion (DRG) and Chronic Pain.

CONTEXT: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. EVIDENCE ACQUISITION: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment. RESULTS: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. CONCLUSIONS: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment.

Comprehensive Review and Update of Burning Eye Syndrome.

Keratoconjunctivitis sicca ("dry eye") is a common (14%-30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as "burning eye syndrome." This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.

Adverse Effects of Recreational and Medical Cannabis.

Purpose of Review: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction. Recent Findings: Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic. Summary: Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use.

Biology of COVID-19 and related viruses: Epidemiology, signs, symptoms, diagnosis, and treatment.

Coronaviruses belong to the family Coronaviridae order Nidovirales and are known causes of respiratory and intestinal disease in various mammalian and avian species. Species of coronaviruses known to infect humans are referred to as human coronaviruses (HCoVs). While traditionally, HCoVs have been a significant cause of the common cold, more recently, emergent viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a global pandemic. Here, we discuss coronavirus disease (COVID-19) biology, pathology, epidemiology, signs and symptoms, diagnosis, treatment, and recent clinical trials involving promising treatments.

Clinical and economic burden of postoperative nausea and vomiting: Analysis of existing cost data.

Postoperative nausea and vomiting (PONV) is an undesirable outcome that occurs in up to 30% of patients. Over the years, the cost of treating PONV has decreased due to the availability of cheaper yet effective antiemetics. Limiting PONV development benefits the hospital system as studies have shown that prevention is associated with shorter post-anesthesia care unit (PACU) stays as well as decreased supply costs and staffing burden. The financial burden for prophylaxis against PONV has been shown to be less than what patients are willing to pay to prevent the development of PONV. Studies have also shown that prevention of initial development of PONV limits readmission rates, which is beneficial to both the patient and the hospital. Owing to recent economic analysis and reductions in antiemetic prices, the patient's preference for comfort, the hospital's commitment to providing the best care, and the system's desire for fiscal prudence are aligned. This culminates in recommending PONV prophylaxis for all patients undergoing anesthesia.

Management of Patients With Chronic Pain in Ambulatory Surgery Centers.

In the setting of increasingly streamlined surgical techniques and perioperative care, the United States healthcare system is seeing a steady rise in the number of procedures being carried out at ambulatory surgery centers. Concurrently, awareness and diagnosis of both chronic pain conditions and substance use disorders have also improved in recent years. As a result of these two shifts, the demographic characteristics of patients undergoing procedures at ambulatory surgery centers are actively evolving. Chronic pain and substance use disorders are difficult to manage in both the outpatient and inpatient settings and present unique challenges in the context of perioperative planning. Both conditions are associated with worsened postoperative outcomes, including refractory pain, decreased functional status, increased length of stay, increased readmission rates, and increased economic costs. There has been a recent movement to include a preoperative risk stratification calculation for these patients, followed by the implementation of enhanced recovery after surgery (ERAS) protocols in these patient cohorts. Taking a step further, patients benefit when standard ERAS protocols are augmented by integrating designated pain specialists into the ambulatory surgery team. This multimodal and multidisciplinary approach must be assessed in the context of the human and financial resources of a given institution and surgery center, but has been shown to improve the quality and safety of perioperative care effectively.

Maximization of Non-Opioid Multimodal Analgesia in Ambulatory Surgery Centers.

Ambulatory surgery centers aid the healthcare system by not only providing a cost-effective option for delivery of care but also by helping to reduce overwhelming case volumes at inpatient facilities. While outpatient protocols have been designed for an increasing number of surgical procedures, the inpatient to outpatient transition of surgery remains limited by both procedure type and patient comorbidities. This limitation stems in part from the heavy emphasis on accelerated discharge following outpatient procedures, given that prolonged recovery time is associated with delayed turnover and increased nursing care demands. Since its inception, enhanced recovery after surgery (ERAS) has aimed to primarily reduce the disruption of physiologic homeostasis that occurs secondary to surgery. More recently, the aim of ERAS has evolved to help transition inpatient procedures to outpatient settings and may even be useful in more emergent cases. It should be noted, however, that outpatient surgery even in combination with ERAS is not the best option for all patients, and the use of ERAS protocols should be complemented with predictive assessments of patient risk. Beyond augmenting the efficiency of outpatient surgery, ERAS protocols, when used in eligible patients and especially when combined with regional anesthetic techniques, are effective in delivering opioid-sparing pain management while increasing overall outcomes and patient satisfaction rates.

An Overview of Current Recommendations and Options for the Management of Cancer Pain: A Comprehensive Review.

It is estimated that one-third of oncologic patients in the USA do not receive analgesia proportional to or adequate for the intensity of their pain. A mechanism-based approach to oncologic pain therapy is critical to ensure that analgesia regimens are individualized and effective. Since the mechanisms that lead to cancer pain are complex, healthcare providers must be willing to elicit and recognize the symptoms of each individual patient since these factors influence both the experience of pain and response to treatment. This process is centered on the use of detailed history in order to understand symptom expression in the context of primary tumor diagnosis and progression, history of cancer pain, psychological distress, sleep disturbances, cognitive function, and addictive behavior. Incorporating all of these factors into the assessment of a patient's pain condition can facilitate management decisions and help predict patient response to treatment.

Investigating the Impact of Gadolinium-Based Contrast Agents on the Corrected QT Interval.

Introduction The manufacturing labels for all currently marketed gadolinium-based MRI contrast agents describe adverse cardiac events reported during post-market use. The goal of this study was to determine prolongation of the rate-corrected QT interval occurs in the immediate setting after gadolinium-based MRI contrast agent injection. Methods This study enrolled adults scheduled to have a gadolinium-based MRI contrast agent injection as part of a diagnostic MRI. A single-lead electrocardiogram was recorded using the AliveCor Kardia® ECG (Mountain View, CA) device before and after injection. The rate-corrected QT interval was subsequently measured by two independent investigators. The QT interval was corrected for rate using the two most common formulas, originally cited by Bazett and Fridericia. These rate-corrected QT intervals from before and after gadolinium-based MRI contrast agent injection were compared using the Wilcoxon signed-rank test paired analysis. Results A total of 24 consenting adults had electrocardiogram that were free of motion artifact. The mean age of the final patient cohort was 59.4 years. There was an equal split of 12 men and 12 women. The mean pre-injection, rate-corrected QT interval, corrected using Bazett's formula, was 395 msec. The mean post-injection, rate-corrected QT interval, corrected using Bazett's formula, was 396 msec. The corrections using Fridericia's formula were 384 and 381 msec, respectively. There was no statistically significant change in Bazett-corrected QT interval (QTc-B) when pre-injection and post-injection values were directly compared. Discussion The results of the present investigation support the conclusion that gadolinium-based MRI contrast agents do not commonly affect rate-corrected QT interval in routine clinical use. While the frequency of rate-corrected QT interval prolongation might be overstated, the severity of adverse events is definitively not. A role for concomitant rate-corrected QT interval-prolonging drugs or unidentified rare factors such as genetic predisposition cannot be ruled out. The limitations of this study include its relatively small size and the implementation of a single-lead electrocardiogram to measure rate-corrected QT interval. Conclusion The present investigation revealed that significant rate-corrected QT interval prolongation, while previously reported in as many as 55% of patients after gadolinium-based MRI contrast agent injection, is not a common occurrence in the routine clinical setting.

A comprehensive review of partial opioid agonists for the treatment of chronic pain.

Chronic pain is a common condition that is being increasingly recognized, diagnosed, and treated in a variety of settings. Opioids can be used to treat chronic pain but at the cost of adverse effects and risk of dependence. Recently, there has been a movement to improve analgesic care in the setting of the opioid epidemic and the overprescribing of opioids, causing over-accessibility, dependence, and large numbers of overdose deaths. Opioid-specific receptors, including the µ, δ, κ, and opioid receptor like-1 (ORL-1) receptors, are each 7-transmembrane spanning proteins, which affect the G-protein and ß-arrestin cascades. Each opioid class can act differently on the receptors, resulting in full, partial, or antagonizing effects. This comprehensive review looks at different agents in major classes, nonselective and mixed/partial agonists/antagonists, including the nonselective partial agonists, levorphanol and tramadol. Mixed partial agonists/antagonists include buprenorphine, pentazocine, nalbuphine, and butorphanol. Oliceridine is the only current selective partial agonist that agonizes specific pathways to promote analgesic effects and discourage adverse effects.

A Comprehensive Review of Slipping Rib Syndrome: Treatment and Management.

Purpose of Review: This is a comprehensive review and update on advances in the understanding and treatment of slipping rib syndrome. It covers the physiology and pathophysiology at the basis of the syndrome, epidemiology and clinical presentation as well as diagnosis. It goes on to review the available literature to provide description and comparison of the available methods for alleviation. Recent Findings: Slipping rib syndrome stems from irritation of intercostal nerves. It is caused by slipping of the costal cartilage and the resulting displacement of a false rib and pinning underneath the adjacent superior rib and nerve irritation. It is rare and spans genders and ages; most evidence about epidemiology is conflicting and mostly anecdotal. Risk factors include trauma and high intensity athletic activity. Presentation is of a sudden onset of pain with jerking motion; the pain can be localized, radiating or diffuse visceral. It is often alleviated by positions that offload the impinged nerve. Diagnosis is clinical, and can be aided by Hooking maneuver and dynamic ultrasound. Definitive diagnosis is with pain relief on nerve block, visualization of altered anatomy during surgery and relief after surgical correction. Initial treatment includes rest, ice and NSAIDs, as well as screening for co-morbid conditions, as well as local symptomatic relief. Injection therapy with local anesthetics and steroids can provide a diagnosis as well as symptomatic relief. Surgical correction remains the definitive treatment. Summary: Slipping rib syndrome is a rare cause of chest pain that could be perceived as local or diffuse pain. Diagnosis is initially clinical and can be confirmed with nerve blocks and surgical visualization. Initial treatment is symptomatic and anti-inflammatory, and definitive treatment remains surgical. More recently, advanced surgical options have paved way for cure for previously hard to treat patients.