Frontline Perspectives on Buprenorphine for the Management of Chronic Pain.

Due to the prevalence of chronic pain and high-impact chronic pain in the US, a significant percentage of the population is prescribed opioids for pain management. However, opioid use disorder is associated with reduced quality of life, along with fatal opioid overdoses, and is a significant burden on the US economy. Considering the clinical needs of patients with intractable chronic pain and the potential harms associated with prescribed and illicit opioids in our communities, having a deep understanding of current treatment options, supporting evidence, and clinical practice guidelines is essential for optimizing treatment selections. Buprenorphine is a Schedule III opioid with a unique mechanism of action, allowing effective and long-lasting analgesia at microgram doses with fewer negative side effects and adverse events, including respiratory depression, when compared with other immediate-release, long-acting, and extended-release prescription opioids. Due to its relatively lower risk for overdose and misuse, buprenorphine was recently added to the Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain as a first-line treatment for chronic pain managed by opioids by the US Departments of Defense and Veterans Affairs, and the Department of Health and Human Services recommends that buprenorphine be made available for the treatment of chronic pain. In this narrative review, we discuss the different buprenorphine formulations, clinical efficacy, advantages for older adults and other special populations, clinical practice guideline recommendations, and payer considerations of buprenorphine and suggest that buprenorphine products approved for chronic pain should be considered as a first-line treatment for this indication.

Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options.

Painful diabetic peripheral neuropathy (DPN) is a highly prevalent and disabling complication of diabetes that is often misdiagnosed and undertreated. The management of painful DPN involves treating its underlying cause via lifestyle modifications and intensive glucose control, targeting its pathogenesis, and providing symptomatic pain relief, thereby improving patient function and health-related quality of life. Four pharmacologic options are currently approved by the US Food and Drug Administration (FDA) to treat painful DPN. These include three oral medications (duloxetine, pregabalin, and tapentadol extended release) and one topical agent (capsaicin 8% topical system). More recently, the FDA approved several spinal cord stimulation (SCS) devices to treat refractory painful DPN. Although not FDA-approved specifically to treat painful DPN, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, gabapentinoids, and sodium channel blockers are common first-line oral options in clinical practice. Other strategies may be used as part of individualized comprehensive pain management plans. This article provides an overview of the most recent US guidelines for managing painful DPN, with a focus on the two most recently approved treatment options (SCS and capsaicin 8% topical system), as well as evidence for using FDA-approved and guideline-supported drugs and devices. Also discussed are unmet needs for this patient population, and evidence for potential future treatments for painful DPN, including drugs with novel mechanisms of action, electrical stimulation devices, and nutraceuticals.

INP104: a drug evaluation of a nonoral product for the acute treatment of migraine.

Migraine is a highly prevalent, disabling neurological disorder that is also associated with gastrointestinal symptoms, autonomic dysfunction and allodynia. Despite the availability of multiple acute agents for migraine, an unmet need remains for effective, well-tolerated drugs that are nonoral and noninvasive. Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate - a molecule with a long history of efficacy familiar to headache specialists - which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD®). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine.

Migraine is a very common headache disorder that often presents with pain and gastrointestinal symptoms. There are many available treatments for migraine, but some patients still need an option that works well for them, that is noninvasive, or does not need to be taken orally. Here we provide a drug evaluation of INP104, an approved acute treatment for migraine that combines a drug and a device: the medication dihydroergotamine (DHE) mesylate, which has been used for decades for treating acute symptoms of migraine, and the Precision Olfactory Delivery (POD^®) device, which delivers DHE mesylate to the hard-to-reach upper regions of the nose. Targeting this region helps medication to be absorbed faster and more consistently. In clinical trials, INP104 demonstrated favorable drug properties, came with few adverse events, and provided fast relief from migraine symptoms.

Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials.

Objective: Treatment outcomes for chronic pain can be poor in patients with depression, anxiety, or insomnia. This analysis evaluated the efficacy and safety of subcutaneous tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), and placebo in patients with osteoarthritis (OA) and a history of these conditions using data from three phase 3 studies.Methods: A post-hoc analysis of data from two pooled placebo-controlled studies and one NSAID-controlled study of subcutaneous tanezumab. All patients had moderate to severe knee or hip OA that was inadequately controlled with standard-of-care analgesics. Efficacy outcomes were least-squares mean change from baseline to Week 16 in Western Ontario McMaster Universities OA Index (WOMAC) Pain, WOMAC Physical Function, Patient's global assessment of OA, and EQ-5D-5L scores. Results were summarized for patients with and without a history of depression, anxiety, or insomnia at baseline.Results: 1545 patients were treated in the pooled placebo-controlled studies (history of depression, 12%; anxiety, 8%; insomnia, 10%; any, 23%) and 2996 in the NSAID-controlled study (16%, 11%, 13%, 28%, respectively). In groups with positive histories, 38-80% took antidepressant or anxiolytic medications at baseline. Within treatments, largely similar improvements in efficacy outcomes were observed in patients with and without a history of depression, anxiety, or insomnia; the types of treatment-emergent adverse events were similar.Conclusions: Patients with OA and a history of depression, anxiety, or insomnia did not appear to experience reduced efficacy outcomes or an altered safety profile in response to tanezumab or NSAID treatment as compared with those without. NCT02697773; NCT02709486; NCT02528188.

Pain and Function in Chronic Musculoskeletal Pain-Treating the Whole Person.

Chronic pain is often associated with functional limitations that have a huge impact on patients' lives. However, despite being relatively common, chronic musculoskeletal pain is still viewed by some as a symptom of another disease rather than its own condition, and is therefore poorly addressed. This is compounded by other challenges in the field, including education gaps for both healthcare professionals and patients, a lack of universal and comprehensive assessment tools, poor societal perceptions of chronic pain, and the current stigma around the use of opioids. Here, we review the current chronic musculoskeletal pain management landscape in the United States and offer professional insight into emerging methods that can be used to improve patient outcomes, in particular, the achievement of meaningful functional goals. This perspective incorporates our combined multidisciplinary (psychiatry, psychology, nursing, physical therapy, and general medicine) experience and insights. We believe that chronic pain is a multifactorial experience and treatment requires an integrated, multidisciplinary approach from a range of healthcare providers. For the best patient outcomes, this team should work together to assess and treat the patient as a whole, addressing their pain and also providing education, empowerment, and support to enable patients to set and achieve meaningful functional goals that will provide real improvement in their quality of life. We believe that the healthcare community should elevate the conversation around chronic musculoskeletal pain management beyond that of just pain, to encompass the meaningful benefits that improvement in functional outcomes brings to patients.

Unmet needs in the acute treatment of migraine attacks and the emerging role of calcitonin gene-related peptide receptor antagonists: An integrative review.

BACKGROUND: Migraine is a prevalent and chronic disease associated with high rates of disability and significant financial and socioeconomic burden. Current acute treatments for migraine attacks include both migraine-specific (e.g., triptans, ergotamines) and nonspecific (e.g., nonsteroidal anti-inflammatory drugs) medications; however, significant unmet treatment needs remain. OBJECTIVES: The authors sought to characterize the nature and drivers of unmet treatment needs in the acute treatment of migraine attacks and describe emerging migraine-specific treatments, that is, calcitonin gene-related peptide (CGRP) receptor antagonists. DATA SOURCES: PubMed searches were conducted using search terms for studies of unmet migraine treatment needs and CGRP receptor antagonists. Additionally, studies presented at recent headache-focused congresses were included. CONCLUSIONS: Forty percent of people with migraine report at least 1 unmet treatment need. Many people are unable to use migraine-specific or nonspecific agents because of contraindications, precautions, and tolerability issues. Disease burden (disability, headache severity/frequency) remains high even in those receiving migraine-specific medications. The oral CGRP receptor antagonists, ubrogepant and rimegepant, demonstrated efficacy in reducing migraine pain, migraine-associated symptoms, and disability, with a low adverse event profile, similar to placebo. IMPLICATIONS FOR PRACTICE: The availability and use of CGRP receptor antagonists may help reduce the extent of unmet needs in the treatment of migraine attacks, resulting in more patients receiving treatment and better outcomes for people with migraine. Nurse practitioners are well positioned to increase rates of migraine diagnosis/treatment (another key unmet need), using consensus guidelines to guide their approach.

Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion.

OBJECTIVE: An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management. METHODS: The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine. RESULTS: The panel recommended that buprenorphine's classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose. CONCLUSIONS: These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.

Cannabinoids in Pain Treatment: An Overview.

The current landscape contains conflicting reports regarding the use of medical marijuana, creating fields of misinformation and lack of understanding by health care providers about cannabinoids. In this article we provide a dispassionate look at medical marijuana, while providing a clinical overview focusing on pain management. We examine the mechanisms of the endocannabinoid system, along with the pharmacology of cannabinoids. Current research on the use of marijuana for the treatment of pain is reviewed. Finally, recommendations for pain management nurses on integrating research, clinical practice, and U.S. drug policy are made.

An overview of abuse-deterrent opioids and recommendations for practical patient care.

Despite advances in the treatment of severe intractable pain, opioids remain a critical and appropriate component of treatment. However, abuse, misuse, and diversion of prescription opioids are significant public health concerns. Opioid abuse-deterrent formulations (ADFs) are one component of an opioid risk management plan to manage patient's pain relief and quality of life while offering some protection against potentially harmful consequences of opioids from misuse and abuse. Opioid ADFs are designed to make manipulation more difficult and administration via non-oral routes less appealing. There are currently nine extended-release and one immediate-release opioid pain medications with US Food and Drug Administration-approved ADF labeling. All use physical/chemical barriers or agonist/antagonist combinations to deter manipulation and abuse. Evidence suggests that opioid ADFs decrease rates of abuse and diversion of opioids in the USA; however, some opioid ADFs are not yet commercially available or have not been on the market long enough to undergo post-marketing data analyses. Opioid ADFs along with the use of prescription drug monitoring programs, clinical assessment tools, toxicology testing, and co-prescribing of naloxone are all tools that can be used to reduce opioid abuse. Patient education on the risks of abuse and diversion is vital and includes a discussion of appropriate use of medication and proper storage. Physician assistants and nurse practitioners are on the "front lines" in battling opioid abuse and serve a key role in recognizing and mitigating the risks of prescription opioid diversion, abuse, and misuse (intentional and unintentional) and in identifying patients at risk for abuse while still providing pain relief to patients.

The pathophysiology, incidence, impact, and treatment of opioid-induced nausea and vomiting.

PURPOSE: Opioid medications are integral in managing acute moderate-to-severe pain. Opioid analgesics bind to µ (mu), κ (kappa), or δ (delta) opioid receptors in the brain, spinal cord, and digestive tract. However, opioids cause adverse effects that may interfere with their therapeutic use. Some adverse effects wane over time, but patients using opioids for acute pain struggle with opioid-induced nausea and vomiting (OINV) the entire time they take the opioid. This article discusses the underlying mechanisms, clinical implications, and treatment strategies of OINV. DATA SOURCES: Systematic search and review of Medline, PubMed, and Google Scholar for articles relating to OINV. In addition, package inserts provided pharmacologic data and dose recommendations as needed. CONCLUSIONS: Research suggests approximately 40% of patients may experience nausea and 15%-25% of patients may experience vomiting after opioid administration. Nausea often precedes vomiting, although they can occur separately. Many patients receiving opioids rate the nausea and vomiting as worse than their pain. Nausea and vomiting can lead to complications including electrolyte imbalances, malnutrition, and volume depletion, and can also negatively affect quality of life and postoperative recovery. IMPLICATIONS FOR PRACTICE: There are several medications that can be used to treat OINV including serotonin receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists. Healthcare providers should be proactive about discussing OINV with patients, as this may improve patient outcomes and pain relief.

Postherpetic neuralgia: epidemiology, pathophysiology, and pain management pharmacology.

Herpes zoster, also known as shingles, is a distinctive clinical condition caused by the reactivation of latent varicella zoster (chickenpox) virus following an initial infection. Approximately 1 million cases of herpes zoster occur annually in the US, and one in every three people develops herpes zoster during their lifetime. Postherpetic neuralgia is a neuropathic pain syndrome characterized by pain that persists for months to years after resolution of the herpes zoster rash. It stems from damage to peripheral and central neurons that may be a byproduct of the immune/inflammatory response accompanying varicella zoster virus reactivation. Patients with postherpetic neuralgia report decreased quality of life and interference with activities of daily living. Approaches to management of postherpetic neuralgia include preventing herpes zoster through vaccination and/or antiviral treatment, and administering specific medications to treat pain. Current guidelines recommend treatment of postherpetic neuralgia in a hierarchical manner, with calcium channel α2-δ ligands (gabapentin and pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline, or desipramine), or topical lidocaine patches as first-line drugs. The safety and tolerability of pharmacologic therapies for pain are important issues to consider as postherpetic neuralgia affects primarily an older population. Patients should be educated on appropriate dosing, titration if applicable, the importance of adherence to treatment for optimal effectiveness, and possible side effects. Health-care professionals play a key role in helping to ameliorate the pain caused by postherpetic neuralgia through early recognition and diligent assessment of the problem; recommending evidence-based treatments; and monitoring treatment adherence, adverse events, responses, and expectations. Nurse practitioners are especially crucial in establishing communication with patients and encouraging the initiation of appropriate pain-relieving treatments.

Diagnosis and treatment for chronic migraine.

Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs.