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Effect of Pain Education and Exercise on Pain and Function in Chronic Achilles Tendinopathy: Protocol for a Double-Blind, Placebo-Controlled Randomized Trial.

Achilles tendinopathy (AT) rehabilitation traditionally includes progressive tendon loading exercises. Recent evidence suggests a biopsychosocial approach that incorporates patient education on psychosocial factors and mechanisms of pain can reduce pain and disability in individuals with chronic pain. This is yet to be examined in individuals with AT.

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Localised neuropathic pain in the primary care setting: a cross-sectional study of prevalence, clinical characteristics, treatment patterns, quality of life and sleep performance.

Localised Neuropathic Pain (LNP) is challenging to diagnose and manage in primary care. To describe clinical characteristics, treatment patterns, quality of life and sleep performance of patients with LNP and estimate its prevalence in primary care. Cross-sectional study in 4 European countries. Patients were identified using a screening tool for LNP. Patients completed the EQ-5D VAS score and Chronic Pain Sleep Inventory (CPSI). There were 1030 LNP patients for analysis. They presented a median pain intensity of 6.0 (IQR 4.0-7.0) with a median duration of 30.9 months (IQR 12.0 – 75.3), despite 97% receiving pain treatment. Main sites affected were the limbs (62% upper/58% lower) and spine (41%). Main aetiologies were neuropathic low back pain (47%), post-surgical neuropathic pain (17%), and diabetic poly-neuropathy (12%). Thirty percent received a single analgesic (2% topical), while combinations comprised 43% systemic-systemic, 24% topical-systemic, 1% topical-topical. Medications included NSAIDs (45%), anticonvulsants (38%), WHO step 2 opioids (35%), and topical analgesics (27%). In the previous 6 months, 40% had switched treatment. The mean (SD) EQ-5D VAS score was 58 (22.3) and the mean (SD) EQ-5D summary score (UK tariff) was 0.62 (0.25). Patients had a CPSI mean index of 41/100, and sleeping pills were used by 33% of patients. The standardised prevalence of LNP by age and sex was 2.01% in the general population and 43.3% among chronic pain patients. Many LNP patients reported pain intensities of six on a ten-point scale in average for durations longer than 2.5 years, with quality of life and sleep performance affected, with frequent treatment combinations and switches, suggesting suboptimal pain management.

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Equity of African American Men in Headache in the United States: A Perspective From African American Headache Medicine Specialists (Part 1).

Migraine and severe headache affect approximately 1 in 6 U.S. adults and migraine is one of the most disabling disorders worldwide. Approximately 903,000 to 1.5 million African American (AA) men are affected by migraine in the United States. Racial disparities in headache medicine exist. In addition, there are limited headache studies that attest to the inclusion of or have robust data on AA men in headache medicine in the United States. Racial concordance between provider and patient may ameliorate some aspects of care disparities. Moreover, it has been demonstrated that diversity and inclusion particularly in leadership of organizations has consistently produced positive change, increased innovation, and long-term success. Most national headache organizations strive to improve the care and lives of people living with headache disorders yet only ~0.5% of their physician members are AA men. Herein, we provide an observation of equity issues from the perspective of AA men in the headache medicine subspecialty. Part 1 of this manuscript explores inherent and potential challenges of the equity of AA men in headache medicine including headache disparities, mistrust, understudied/lack of representation in research, cultural differences, implicit/explicit bias, and the diversity tax. Part 2 of this work offers possible solutions to achieve equity for AA men in headache including: (1) addressing head and facial pain disparities and mistrust in AA men; (2) professionalism and inclusion; (3) organizational/departmental leadership buy-in for racial diversity; (4) implicit/explicit and other bias training; (5) diversity panels with open discussion; (6) addressing diversity tax; (7) senior mentorship; (8) increased opportunities for noteworthy and important roles; (9) forming and building alliances and partnerships; (10) diversity leadership training programs; (11) headache awareness, education, and literacy with focus to underrepresented in medicine trainees and institutions; and (12) focused and supported the recruitment of AA men into headache medicine. More work is needed for equity of AA men in headache medicine.

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Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology.

The kappa opioid receptor (KOR) is a G protein-coupled receptor (GPCR) that can signal through multiple signaling pathways. KOR agonists are known to relieve pain and itch, as well as induce dysphoria, sedation, hallucinations, and diuresis. As is the case with many other GPCRs, specific signaling pathways downstream of the KOR have been linked to certain physiological responses induced by the receptor. Those studies motivated the search and discovery of a number of KOR ligands that preferentially activate one signaling pathway over another. Such compounds are termed functionally selective or biased ligands, and may present a way of inducing desired receptor effects with reduced adverse reactions. In this chapter, I review the molecular intricacies of KOR signaling and discuss the studies that have used biased signaling through the KOR as a way to selectively modulate in vivo physiology.

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Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study.

Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with multiple sclerosis (MS), and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected via a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia survey criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N=842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief were reported. Cannabis use for pain was more common and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAIDs use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches.

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Sex-dependent effects of an Hnrnph1 mutation on fentanyl addiction-relevant behaviors but not antinociception in mice.

Opioid Use Disorder (OUD) and opioid-related deaths remain a major public health concern in the United States. Both environmental and genetic factors influence risk for OUD. We previously identified Hnrnph1 as a quantitative trait gene underlying the stimulant, rewarding, and reinforcing properties of methamphetamine. Prior work demonstrates that hnRNP H1, the RNA-binding protein encoded by Hnrnph1, post-transcriptionally regulates Oprm1 (mu opioid receptor gene) – the primary molecular target for the therapeutic and addictive properties of opioids. Because genetic variants can exert pleiotropic effects on behaviors induced by multiple drugs of abuse, in the current study, we tested the hypothesis that Hnrnph1 mutants would show reduced behavioral sensitivity to the mu opioid receptor agonist fentanyl. Hnrnph1 mutants showed reduced sensitivity to fentanyl-induced locomotor activity, along with a female-specific reduction in, and a male-specific induction of, locomotor sensitization following three, daily injections (0.2 mg/kg, i.p.). Hnrnph1 mutants also required a higher dose of fentanyl to exhibit opioid reward as measured via conditioned place preference. Male Hnrnph1 mutants showed reduced fentanyl reinforcement. Hnrnph1 mutants also showed reduced sucrose motivation, suggesting a reward deficit. No genotypic differences were observed in baseline thermal nociception, fentanyl-induced antinociception, physical or negative affective signs of opioid dependence, or in sensorimotor gating. In the context of our prior work, these findings suggest that Hnrnph1 dysfunction exerts a selective role in reducing the addiction liability to drugs of abuse (opioids and psychostimulants), which could provide new biological pathways to improve their therapeutic profiles.

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Improving outcomes and decreasing costs for neurological diseases: mind the gap.

Neurological disorders are the leading cause of disability-adjusted life years (DALYs) and the second leading cause of deaths. The four large contributors of neurological DALYs are stroke, migraine, dementia and meningitis [1]. Global and regional actions to decrease this burden are urgently needed. To appropriately set priorities and allocate resources for such actions, political leaders need to be informed by epidemiological and health economic studies.

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Implementation and Policy Recommendations from the VHA State-of-the-Art Conference on Strategies to Improve Opioid Safety.

Evidence-based treatment of opioid use disorder, the prevention of opioid overdose and other opioid-related harms, and safe and effective pain management are priorities for the Veterans Health Administration (VHA). The VHA Office of Health Services Research and Development hosted a State-of-the-Art Conference on "Effective Management of Pain and Addiction: Strategies to Improve Opioid Safety" on September 10-11, 2019. This conference convened a multidisciplinary group to discuss and achieve consensus on a research agenda and on implementation and policy recommendations to improve opioid safety for Veterans. Participants were organized into three workgroups: (1) managing opioid use disorder; (2) Long-term opioid therapy and opioid tapering; (3) managing co-occurring pain and substance use disorder. Here we summarize the implementation and policy recommendations of each workgroup and highlight important cross-cutting issues related to telehealth, care coordination, and stepped care model implementation.

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Association Between Opioid Dose Reduction Against Patients’ Wishes and Change in Pain Severity.

There is inadequate evidence of long-term benefit from opioid medications for chronic pain and substantial evidence of potential harms. For patients, dose reduction may be beneficial when implemented voluntarily and supported by a multidisciplinary team but experts have advised against involuntary opioid reduction.

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Benefits and Harms of Long-term Opioid Dose Reduction or Discontinuation in Patients with Chronic Pain: a Rapid Review.

Many clinicians are reevaluating the use of long-term opioid therapy (LTOT) for chronic pain in response to the opioid crisis and calls from organizations including the Centers for Disease Control & Prevention to limit prescribing of high-dose opioids. However, this practice change is occurring largely in the absence of data regarding patient outcomes. A 2017 systematic review found inconclusive evidence on the impact of LTOT dose reduction and discontinuation on pain severity and function, quality of life, withdrawal symptoms, substance abuse, and adverse effects. This rapid systematic review provides an updated evidence synthesis of patient outcomes following LTOT dose reduction including serious harms such as overdose and suicide.

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