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Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations.
Learn More >Psychosocial variables are key factors influencing psycho-physical equilibrium in migraine patients. Social isolation and vulnerability to stressors may prevent efficient psychological adjustment negatively affecting adaptation to life changes, as that imposed during Covid-19 lockdown. Here, we explored psychosocial dimensions and changes in clinical condition during Covid-19 lockdown in migraine patients, with regard to migraine type and headache impact.
Learn More >Reactive nitroxidative species, such as nitric oxide but particularly peroxynitrite, have been strongly implicated in pain mechanisms. Targeting peroxynitrite is anti-nociceptive in pain models, but little is known about its role in migraine mechanisms. Given the need to validate novel targets for migraine headache, our objective was to study the potential of reactive nitroxidative species, particularly peroxynitrite, as novel targets for drug discovery and their role in migraine mechanisms.
Learn More >Cluster headache is a severe primary headache disorder commonly featuring a strikingly distinct circadian attack pattern. Therefore, the circadian system has been suggested to play a crucial role in the pathophysiology of cluster headache. Cryptochromes are key components of the molecular clock generating circadian rhythms and have previously been shown to be associated with several psychiatric disorders, including seasonal affective disorder, bipolar disorder, and depression.
Learn More >To assess the effectiveness of a pain e-consult program (PEP), a multidisciplinary telementoring service based on the ECHO model to reduce opioid use, in the outpatient setting.
Learn More >Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.
Learn More >To determine if a clinical presentation indistinguishable from migraine can occur due to an underlying condition or pathology, that is, "symptomatic migraine."
Learn More >Previous reviews of mobile messaging for individuals with musculoskeletal pain have shown positive effects on pain and disability. However, the configuration of digital content, method of presentation and interaction, dose and frequency needed for optimal results remain unclear. Patient preferences concerning such systems are also unclear. Addressing these knowledge gaps, incorporating evidence from both experimental and observational studies, may be useful to understand the extent of the relevant literature, and to influence the design and outcomes of future messaging systems. We aim to map information that could be influential in the design of future mobile messaging systems for individuals with musculoskeletal pain conditions, and to summarise the findings of efficacy, effectiveness, and economics derived from both experimental and observational studies.
Learn More >Pressure pain thresholds (PPTs) are commonly assessed to quantify mechanical sensitivity in various conditions, including migraine. Digital and analogue algometers are used, but the concurrent validity between these algometers is unknown. Therefore, we assessed the concurrent validity between a digital and analogue algometer to determine PPTs in healthy participants and people with migraine.
Learn More >Delineating the Ligand-Receptor Interactions That Lead to Biased Signaling at the μ-Opioid Receptor.
Biased agonists, which selectively stimulate certain signaling pathways controlled by a G protein-coupled receptor (GPCR), hold great promise as drugs that maximize efficacy while minimizing dangerous side effects. Biased agonists of the μ-opioid receptor (μOR) are of particular interest as a means to achieve analgesia through G protein signaling without dose-limiting side effects such as respiratory depression and constipation. Rational structure-based design of biased agonists remains highly challenging, however, because the ligand-mediated interactions that are key to activation of each signaling pathway remain unclear. We identify several compounds for which the and enantiomers have distinct bias profiles at the μOR. These compounds serve as excellent comparative tools to study bias because the identical physicochemical properties of enantiomer pairs ensure that differences in bias profiles are due to differences in interactions with the μOR binding pocket. Atomic-level simulations of compounds at μOR indicate that and enantiomers adopt different poses that form distinct interactions with the binding pocket. A handful of specific interactions with highly conserved binding pocket residues appear to be responsible for substantial differences in arrestin recruitment between enantiomers. Our results offer guidance for rational design of biased agonists at μOR and possibly at related GPCRs.
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