Treatment and Management of Xiphoidalgia.

Xiphodynia is a rare but debilitating condition that can be described as a form of pain on the xiphisternal joint or any related structures that are anchored to the xiphoid process. Although xiphodynia is a musculoskeletal pain in nature, the pain located in the anterior chest can commonly mislead physicians into pursuing other diagnoses such as cardiac diseases. This leads to a prolonged duration of pain before receiving treatment. In the attempt to alleviate pain resulting from this condition, physicians have previously utilized a range of treatment options, including conservative management, injections, or in severe cases, xiphoidectomy. In this review, we aim to give a brief overview of xiphodynia, including clinical diagnoses and current treatment modalities. Key Summary Points: 1. Xiphodynia can be described as pain radiating from an irritated xiphoid process that can travel to the chest, abdomen, throat, and arms2. Risk factors for developing secondary xiphoidalgia include GERD, gall-bladder disease, angina pectoris, and coronary-artery disease3. The treatment of xiphodynia can range from conservative management to injections or a xiphoidectomy4. Further research is required to develop a standardized treatment protocol and currently the choice of treatment depends on the patient's individual case and the degree of severity.

Review of Interventional Therapies for Refractory Pediatric Migraine.

This is a review of the latest and seminal evidence in pediatric migraine. It covers the etiology and pathophysiology known today, and then will review treatment options, efficacy and safety, quality of data and indications. Though migraine is usually regarded as an infliction in adults, it is not uncommon in the pediatric population and affects up to 8% of children. Children may experience migraine differently than adults, and present not only with headache but also frequent gastrointestinal symptoms. They are frequently shorter in duration than in adults. Traditional migraine treatment in adults is less effective in children. In this population, adjunct therapies - such as interventional techniques - should be considered when traditional treatment fails, including Botulinum Toxin A (BTA) injections, peripheral nerve and ganglion blocks. BTA injections are FDA approved for migraine prophylaxis in adults, but currently not in children; however, recent evidence shows efficacy and safety in pediatric migraine management. Nerve blocks stop nociceptive afferent fibers through injection of local anesthetics, and it may be associated with the local injection of corticosteroids. Although more common in adults, recent data suggests they are safe and effective in children and adolescents. Blocking the sphenopalatine ganglion can be achieved through nasal approach, and achieves a similar action by blocking the entire ganglion. Interventional techniques may provide a key component in the alleviation of this otherwise debilitating chronic migraine pain. Though most studies have been performed in adults, new studies provide encouraging results for treatment in children.

Inotersen to Treat Polyneuropathy Associated with Hereditary Transthyretin (hATTR) Amyloidosis.

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients. Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place. Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level.

A Comprehensive Update of the Treatment and Management of Bertolotti's Syndrome: A Best Practices Review.

Bertolotti's Syndrome is defined as chronic back pain caused by transitional lumbosacral vertebra. The transitional vertebra may present with numerous clinical manifestations leading to a myriad of associated pain types. The most common is pain in the sacroiliac joint, groin, and hip region and may or may not be associated with radiculopathy. Diagnosis is made through a combination of clinical presentations and imaging studies and falls into one of four types. The incidence of transitional vertebra has a reported incidence between 4 and 36%; however, Bertolotti's Syndrome is only diagnosed when the cause of pain is attributed to this transitional anatomy. Therefore, the actual incidence is difficult to determine. Initial management with conservative treatment includes medical management and physical therapy. Injection therapy has been established as an effective second line. Epidural steroid injection at the level of the transitional articulation is effective, with either local anesthetics alone or in combination with steroids. Surgery carries higher risks and is reserved for patients failing previous lines of treatment. Options include surgical removal of the transitional segment, decompression of stenosed foramina, and spinal fusion. Recent evidence suggests that radiofrequency ablation (RFA) around the transitional segment may also provide relief. This manuscript is a comprehensive review of the literature related to Bertolotti's Syndrome. It describes the background, including epidemiology, pathophysiology, and etiology of the Syndrome, and presents the best evidence available regarding management options. Bertolotti's Syndrome is considered an uncommon cause of chronic back pain, though the actual incidence is unclear. Most evidence supporting these therapies is of lower-level evidence with small cohorts, and more extensive studies are required to provide strong evidence supporting best practices.

A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee.

PURPOSE OF REVIEW: The purpose of this systematic review is to discuss emerging evidence in the field of viscosupplementation for chronic knee pain secondary to Osteoarthritis (OA). This review focuses on types of viscosupplementation that are clinically available currently, evidence to support their use, contraindications, and adverse events. RECENT FINDINGS: OA, also known as degenerative joint disease, is the most common form of arthritis in the United States, affecting 54.4 million, or 22.7% of the adult population. The knee is the most common joint affected in OA, with up to 41% involvement, 30% in the hands, and 19% in the hips. The pathophysiology of OA is complex, with contributing factors including mechanical stress to the joint, as well as many person-specific factors such as genetic susceptibility, ethnicity, nutrition, and sex. Treatment modalities include weight control, exercise, non-steroidal and steroidal anti-inflammatory drugs, opioids, intra-articular platelet-rich plasma, placebo, corticosteroid injection, intra-articular viscosupplementation, and surgery. Viscosupplementation consists of injection of hyaluronic acid (HA) into affected joints, intending to restore the physiologic viscoelasticity in the synovial fluid (SF) in the absence of inflammation. HA has also been shown to downregulate pro-inflammatory factors, such as PGE2 and NFkB, and proteases and proteinases known to break down the joint matrix.The contraindications for HA injection are similar to any other injection therapy, and adverse events are usually mild, local, and transient. Viscosupplementation (VS) is effective over placebo and more effective than NSAIDs and corticosteroids in pain reduction and improved functionality; however, guidelines recommend neither for nor against its use, demonstrating variability in the existing evidence base.Current VS options divide primarily into native vs. cross-linked and low-molecular-weight vs. high-molecular-weight. Current treatment options include Hylan g-f-20, Sodium Hyaluronate preparations (Suparts Fx, Euflexxa, Gelsyn-3, Durolane, Hyalgen), single-use agents (Gel-One, Synvisc-One, Monovisc), and Hyaluronan (Orthovisc, Monovisc, Hymovic). They share a common safety profile, and all have evidence supporting their efficacy. Their specific details are reviewed here. SUMMARY: OA is the most common form of arthritis. It is a chronic, debilitating illness with a high impact on the functionality and quality of life of a significant part of the population in the western world. Treatments include medical management, physical therapy, activity modification, injection, and surgery. VS effectively reduces pain, increases functionality, and delays surgery in the knee to treat osteoarthritis. While previous studies have demonstrated variable results, more evidence is becoming available generally supportive of the benefit of VS in the treatment of knee OA.

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.

Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada.

PURPOSE: To evaluate the epidemiology, presentation and management of hypoparathyroidism in Canada. Hypoparathyroidism is associated with significant morbidity and poor quality of life. We present baseline results from the Canadian National Hypoparathyroidism Registry, a prospective observational study evaluating hypoparathyroidism in Canada. METHODS: Our study enrolled 130 patients with hypoparathyroidism. Patients were followed every 6 months with clinical and lab assessments. We present baseline data in this manuscript. RESULTS: Seventy percent (91/130) of patients had postsurgical hypoparathyroidism, 30% (39/130) of patients had nonsurgical hypoparathyroidism due to autoimmune, genetic or idiopathic causes, and a molecular diagnosis was confirmed in 11 of these 39 patients. Pseudohypoparathyroidism was confirmed in 4/39 patients, DiGeorge syndrome in 2/39 patients, Barakat syndrome with a mutation in the GATA3 gene in 1/39, and activating mutations of the CASR gene in 3/39 patients with nonsurgical hypoparathyroidism. Renal complications with nephrocalcinosis or nephrolithiasis were present in 27% (14/52) of patients with postsurgical disease and 17% (4/24) of patients with nonsurgical hypoparathyroidism. Basal ganglia calcification was noted on imaging in 15% (n = 5/34) of patients with postsurgical hypoparathyroidism and 37% (n = 7/19) of patients with nonsurgical hypoparathyroidism. CONCLUSIONS: Hypercalciuria was more commonly seen in those with renal complications of nephrocalcinosis, nephrolithiasis or CKD, and hyperphosphatemia was more commonly seen in those with basal ganglia calcification. Hospitalization occurred in 28% of those with postsurgical hypoparathyroidism and 46% of those with nonsurgical hypoparathyroidism. Hypoparathyroidism is associated with significant morbidity. Effective strategies to reduce the short-and long-term complications of hypoparathyroidism need to be developed and evaluated.

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.

Treatment and Management of Twelfth Rib Syndrome: A Best Practices Comprehensive Review.

BACKGROUND: Twelfth rib syndrome, or slipping of the 12th rib, is an often overlooked cause for chronic chest, back, flank, and abdominal pain from irritation of the 12th intercostal nerve. Diagnosis is clinical and follows the exclusion of other causes of pain. This syndrome is usually accompanied by long-suffering, consequent psychiatric comorbidities, and increased health care costs, which are secondary to the delayed diagnosis. OBJECTIVES: This manuscript is a review of twelfth rib syndrome and its management options. The review provides etiology, pathophysiology, and epidemiology of twelfth rib syndrome. Additionally, diagnosis and current options for treatment and management are presented. STUDY DESIGN: This is a narrative review of twelfth rib syndrome. SETTING: A database review. METHODS: A PubMed search was conducted to ascertain seminal literature regarding twelfth rib syndrome. RESULTS: Conservative treatment is usually the first line, including local heat or ice packs, rest, and oral over-the-counter analgesics. Transcutaneous stimulation and 12th intercostal nerve cryotherapy have also been described with some success. Nerve blocks can additionally be tried and are usually effective in the immediate term; there is a paucity of evidence to suggest long-term efficacy. Surgical removal of all or part of the 12th rib and possibly the 11th rib, as well as the next line of therapy, may provide long-lasting relief of pain. LIMITATIONS: Further large scale clinical studies are needed to assess the most effective management of twelfth rib syndrome. CONCLUSIONS: Twelfth rib syndrome is usually diagnosed late and causes significant morbidity and suffering. The actual epidemiology is unclear given the difficulty of diagnosis. Nerve blocks and surgical rib resection appear to be effective in treating this syndrome, however, further evidence is required to properly evaluate them. Familiarity with this syndrome is crucial in reaching a prompter diagnosis.

A Comprehensive Review of Over the Counter Treatment for Chronic Low Back Pain.

PURPOSE OF THE REVIEW: Chronic low back pain (CLBP) is a major contributor to societal disease burden and years lived with disability. Nonspecific low back pain (LBP) is attributed to physical and psychosocial factors, including lifestyle factors, obesity, and depression. Mechanical low back pain occurs related to repeated trauma to or overuse of the spine, intervertebral disks, and surrounding tissues. This causes disc herniation, vertebral compression fractures, lumbar spondylosis, spondylolisthesis, and lumbosacral muscle strain. RECENT FINDINGS: A systematic review of relevant literature was conducted. CENTRAL, MEDLINE, EMBASE, PubMed, and two clinical trials registry databases up to 24 June 2015 were included in this review. Search terms included: low back pain, over the counter, non-steroidal anti-inflammatory (NSAID), CLBP, ibuprofen, naproxen, acetaminophen, disk herniation, lumbar spondylosis, vertebral compression fractures, spondylolisthesis, and lumbosacral muscle strain. Over-the-counter analgesics are the most frequently used first-line medication for LBP, and current guidelines indicate that over-the-counter medications should be the first prescribed treatment for non-specific LBP. Current literature suggests that NSAIDs and acetaminophen as well as antidepressants, muscle relaxants, and opioids are effective treatments for CLBP. Recent randomized controlled trials also evaluate the benefit of buprenorphine, tramadol, and strong opioids such as oxycodone. This systematic review discusses current evidence pertaining to non-prescription treatment options for chronic low back pain.

Use of cannabidiol (CBD) for the treatment of chronic pain.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

An evidence-based review of neuromodulation for the treatment and management of refractory angina.

Angina pectoris is defined as substernal chest pain that is typically exacerbated by exertion, stress, or other exposures. There are various methods of treatment for angina. Lifestyle modification and pharmacological management are considered as conservative treatments. If these medications do not result in the resolution of pain, more invasive approaches are an option, like coronary revascularization. Refractory angina (RA) is differentiated from acute or chronic angina based on the persistence of symptoms despite conventional therapies. Overall, the prevalence of RA is estimated to be 5%-15% in patients with coronary artery disease, which can account for up to 1,500,000 current cases and 100,000 new cases in the United States per year. Spinal cord stimulation treatment is a viable option for patients who are suffering from RA pain and are either not candidates for revascularization surgery or are currently not being well managed on more traditional treatments. Many studies show a positive result.

An Evidence-Based Review of Galcanezumab for the Treatment of Migraine.

PURPOSE OF REVIEW: This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options. RECENT FINDINGS: Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

Tarlov cysts in a 49-year-old woman presenting with bilateral lower-extremity radiculopathy: A case report.

Tarlov cysts are an uncommon and often incidentally noted source of low back pain in women. Because these cysts can be asymptomatic, they can be overlooked on radiological imaging. This case is of a 49-year-old woman who presented with a chronic history of low back pain and bilateral radiculopathy who on magnetic resonance imaging (MRI) was found to have multiple Tarlov cysts. This case illustrates the need for large observational studies to show the incidence of Tarlov cysts as a cause of low back pain in women.

The Utility of Percutaneous Balloon Kyphoplasty for Treatment of Traumatic Vertebral Compression Fracture to Prevent Opioid Dependence in a Young Opioid-Dependent Patient.

Vertebral compression fractures are often found in the elderly population with known risk factors. Less commonly, they may occur in otherwise healthy patients following traumatic falls and can cause significant pain requiring opioid therapy. This case emphasizes the use of percutaneous balloon kyphoplasty as an effective treatment strategy in a young opioid-dependent patient as a means to support the return to baseline functionality.

A Comprehensive Update of Lofexidine for the Management of Opioid Withdrawal Symptoms.

Purpose of Review: This is a comprehensive review of the literature regarding the use of Lofexidine for opiate withdrawal symptoms. It covers the background and necessity of withdrawal programs and the management of withdrawal symptoms and then covers the existing evidence of the use of Lofexidine for this purpose. Recent Findings: Opiate abuse leads to significant pain and suffering. However, withdrawal is difficult and often accompanied by withdrawal symptoms and renewed cravings. These symptoms are driven mostly by signaling in the locus coeruleus and the mesolimbic system and a rebound increase in noradrenaline, producing symptoms such as anxiety, gastrointestinal upset, and tension. Lofexidine, an alpha-2 agonist, can be used to manage acute withdrawal symptoms before starting maintenance treatment with either methadone or buprenorphine. Lofexidine, if FDA approved for management of withdrawal symptoms and has been proved to be both effective and safe. Summary: Opiate addiction is increasing and plaguing the western world and specifically the U.S. It takes a large toll on both a personal and societal level and carries a high cost. Withdrawal is difficult, both related to withdrawal symptoms and renewed cravings. Lofexidine has been shown to be effective in reducing the former and could potentially aid in recovery and withdrawal.

Naldemedine for the Use of Management of Opioid Induced Constipation.

Purpose of Review: Opioid medications are a pillar of acute and chronic analgesia, though their use is often accompanied by side-effects, such as opioid-induced constipation. Unfortunately, tolerance rarely develops to this untoward side effect. This review presents the background, evidence, and indications for the use of Naldemedine (Brand name Symproic 0.2 mg tablets) to treat opioid-induced constipation. Recent Findings: Opioids are often used for the treatment of acute and chronic analgesia. Outside of the central effect they exert, they also interact with peripheral receptors, resulting in opioid-induced constipation, the commonest of side effects of chronic opioid usage. Complications include colonic distention, ileus, perforation, and can progress to other serious bowel complications, which can result in hospitalization and fatal events.For the most part, laxatives and other anti-constipation therapies are often inefficient and require intervention directed at the root cause, such as peripheral mu receptor agonists, including methylnaltrexone, naloxegol, and naldemedine. Naldemedine is the most recent to gain FDA approval of the group.An antagonist of Mu, Kappa, and Delta peripheral receptors, Naldemedine, is the only drug to counteract all three receptor classes. It was shown to be both safe and effective when compared with placebo. No data exists to compare its efficacy to that of other members of the group. Summary: Opioids are frequently used in the management of acute and chronic pain. The most common of the side effects is opioid-induced constipation, secondary to the peripheral activity of opioids. Naldemedine is an FDA-approved, once-daily oral tablet that counteracts this side effect by antagonizing mu, kappa, and delta-opioid receptors and has been shown to be safe and effective. Further investigation including head-to-head clinical trials are required to evaluate the relative efficacy of naldemedine compare with other peripheral opiate receptor antagonists.