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Musculoskeletal (MSK) pain represents a considerable worldwide healthcare burden. This study aimed to gain consensus from practitioners who work with MSK pain patients, on the most appropriate primary care treatment options for subgroups of patients based on prognostic risk of persistent disabling pain. Agreement was sought on treatment options for the five most common MSK pain presentations: back, neck, knee, shoulder and multisite pain, across three risk subgroups: low, medium and high.
Learn More >Migraine is the most common of all neurological disorders. A breakthrough in migraine treatment emerged in the early nineties with the introduction of 5-HT1B/D receptor agonists called triptans. Triptans are used as the standard of care for acute migraine; however, they have significant limitations such as incomplete and inconsistent pain relief, high rates of headache recurrence, class- specific side effects and cardiovascular contraindications. First- and second-generation calcitonin gene-related peptide (CGRP) receptor antagonists, namely gepants, is a class of drugs primarily developed for the acute treatment of migraine. CGRP is the most evaluated target for migraine treatments that are in development. Areas covered: This article reviews the available data for first- and second-generation CGRP receptor antagonists, the role of CGRPs in human physiology and migraine pathophysiology and the possible mechanism of action and safety of CGRP targeted drugs. Expert opinion: Available data suggest that second generation of gepants has clinical efficacy similar to triptans and lasmiditan (5-HT1F receptor agonist) and has improved tolerability. Future studies will assess their safety, especially in specific populations such as patients with cardiovascular disease and pregnant women.
Learn More >Approximately 10% of pediatric patients have recurrent headaches, with migraine being the most common headache type. If untreated, migraine may progress to status migrainosus, a debilitating condition of prolonged duration, high pain severity, and significant disability. There is high variability in the treatment of status migrainosus including medications used and treatment setting, which may occur in the emergency room, as an inpatient admission, or, less often, in an outpatient infusion center. The paucity of research on the treatment of status migrainosus is a limitation to treatment effectiveness.
Learn More >Despite the serious side effects, analgesics acting on opioid receptors are still considered the best way to get antinociception. Matrix metalloproteinases, a large family of zinc-dependent proteases implicated in many pathological conditions, such as diabetes and osteoarthritis, are also involved in inflammation and pain. Methodology & results: Looking for evidence of possible interactions of opioid pathways and inflammation mediators, molecular modeling studies of a series of recently developed μ-opioid receptor benzomorphanic agonists together with biological data on pain and inflammation molecular targets, allowed us to hypothesize a possible correlation between μ-opioid receptor system and MMP-9.
Learn More >Migraine is a primary headache disorder and one of the most common and disabling neurological diseases worldwide. Genome-wide association studies have identified ≈40 genetic loci associated with migraine. How these and other genetic findings are used to expand our knowledge on the pathophysiological mechanism of common migraine and rare migraine variants will be discussed.
Learn More >A relationship between sleep and pain is well established. A better understanding of the mechanisms that link sleep and pain intensity is urgently needed to optimise pain management interventions. The objective of this systematic review was to identify, synthesise and critically appraise studies that have investigated putative mediators on the path between sleep and pain intensity.
Learn More >Exchange protein directly activated by cAMP (Epac) and protein kinase A are effectors for cAMP with distinct actions and regulatory mechanisms. Epac is a Rap guanine nucleotide exchange factor that activates Rap1; protein kinase C (PKC) is a major downstream target of Epac-Rap1 signaling that has been implicated in a variety of pathophysiological processes, including cardiac hypertrophy, cancer, and nociceptor sensitization leading to chronic pain. Despite the implication of both Epac and PKC in these processes, few downstream targets of Epac-PKC signaling have been identified. This study characterized the regulation of PKC activity downstream of Epac activation. Using an antibody that recognizes phospho-serine residues within the consensus sequence phosphorylated by PKC, we analyzed the 1-dimensional banding profile of PKC substrate protein phosphorylation from the Neuro2A mouse neuroblastoma cell line. Activation of Epac either indirectly by prostaglandin PGE2, or directly by 8-pCPT-2-O-Me-cAMP-AM (8pCpt), produced distinct PKC phospho-substrate protein bands that were suppressed by co-administration of the Epac inhibitor ESI09. Different PKC isoforms contributed to the induction of individual phospho-substrate bands, as determined using isoform-selective PKC inhibitors. Moreover, the banding profile after Epac activation was altered by disruption of the cytoskeleton, suggesting that the orchestration of Epac-dependent PKC signaling is regulated in part by interactions with the cytoskeleton. The approach described here provides an effective means to characterize Epac-dependent PKC activity.
Learn More >There are no community-based studies investigating the association between sleep duration and postherpetic neuralgia (PHN) development. The aim of the current study was to examine the association of sleep with herpes zoster (HZ) incidence and PHN.
Learn More >Spinal health depends on optimal back muscle performance, and this is determined by muscle structure and function. There has been substantial research evaluating the differences in structure and function of many back muscles, including the multifidus and erector spinae, but with considerable variation in results. Many studies have shown atrophy, fat infiltration, and connective tissue accumulation in back muscles, particularly deep fibers of the multifidus, but the results are not uniform. In terms of function, results are also somewhat inconsistent, often reporting lower multifidus activation and augmented recruitment of more superficial components of the multifidus and erector spinae, but, again, with variation between studies. A major recent observation has been the identification of time-dependent differences in features of back muscle adaptation, from acute to subacute/recurrent to chronic states of the condition. Further, these adaptations have been shown to be explained by different time-dependent mechanisms. This has substantial impact on the rationale for rehabilitation approaches. The aim of this commentary was to review and consolidate the breadth of research investigating adaptation in back muscle structure and function, to consider explanations for some of the variation between studies, and to propose how this model can be used to guide rehabilitation in a manner that is tailored to individual patients and to underlying mechanisms. .
Learn More >Pain impacts the lives of millions of community-dwelling older adults. An important characteristic of pain is "pain interference" which describes the influence of pain on function. A description of pain interference is limited in rural settings where the number of older adults is expected to increase, and health disparities exist.
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