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Central sensitization in migraine is related to restless legs syndrome.

We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS).

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Treatment patterns and medication adherence among newly diagnosed patients with migraine: a drug utilisation study.

Prophylactic drugs currently used for migraine treatment are not specific. Furthermore, few studies in existing literature describe drugs utilisation patterns and adherence to migraine prophylactic treatment. This study is aimed to describe utilisation patterns of migraine drugs, evaluate adherence to prophylactic medications and investigate drug-related costs.

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Equity of African American Men in Headache in the United States: A Perspective From African American Headache Medicine Specialists (Part 2).

In part 1 of this opinion piece, we described inherent and potential challenges of the equity of African American (AA) men in headache medicine including headache disparities, mistrust, understudied/lack of representation in research, cultural differences, implicit/explicit bias, and the diversity tax. We shared personal experiences related to headache medicine likely faced due to the color of our skin. In part 2, we offer 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 a focus to underrepresented in medicine trainees and institutions; and (12) focused and supported the recruitment of AA men into headache medicine.

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NMDA receptors in axons: there’s no coincidence.

In the textbook view, N-methyl-D-aspartate (NMDA) receptors are postsynaptically located detectors of coincident activity in Hebbian learning. However, controversial presynaptically located NMDA receptors (preNMDARs) have for decades been repeatedly reported in the literature. These preNMDARs have typically been implicated in the regulation of short-term and long-term plasticity, but precisely how they signal and what their functional roles are have been poorly understood. The functional roles of preNMDARs across several brain regions and different forms of plasticity can differ vastly, with recent discoveries showing key involvement of unusual subunit composition. Increasing evidence shows preNMDAR can signal through both ionotropic action by fluxing calcium and metabotropic mode even in the presence of magnesium blockade. We argue that these unusual properties may explain why controversy has surrounded this receptor type. In addition, the expression of preNMDARs at some synapse types but not others can underlie synapse-type-specific plasticity. Last but not least, preNMDARs are emerging therapeutic targets in disease states such as neuropathic pain. We conclude that axonally located preNMDARs are required for specific purposes and do not end up there by accident.

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Safety of Low-Dose Tanezumab in the Treatment of Hip or Knee Osteoarthritis: A Systemic Review and Meta-analysis of Randomized Phase III Clinical Trials.

To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA).

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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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