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The highest prevalence of migraine is detected among people who are of working age. The aim of this study was to assess the burden of migraine in an occupational health care setting using real world data collected as a part of routine clinical practice.
Learn More >Low back pain is one of the most prevalent musculoskeletal conditions and the highest contributor to disability in the world. It is characterized by frequent relapses leading to additional care-seeking. Engagement in leisure physical activity is associated with lower recurrences and better prognosis and potentially reduced care-seeking. Our aim was to investigate the feasibility and preliminary efficacy of a patient-centred physical activity intervention, supported by health coaching and mobile health, to reduce care-seeking, pain and disability in patients with chronic low back pain after treatment discharge.
Learn More >Migraine is a prevalent disease with a substantial socioeconomic impact. However, stigma affects social attitude toward migraine, accruing additional burden on individuals with migraine and isolating them from a society that should be supporting them. PURPOSE OF THIS REVIEW: This review will discuss the following concepts: (1) the emergence of stigma toward migraine and its impact on medical care; (2) internalized stigma among those with migraine and its detrimental effect on quality of life and patient-physician relationships; (3) the structural impact of stigma on research funding, workplace support, and specialized care; and (4) strategies for "rebranding" the disease and alleviating stigma toward migraine. RECENT FINDINGS: Recent literature on condition rebranding offers strategies on how to define and communicate migraine to the public. Rebranding of migraine to alleviate societal stigma is paramount. This involves use of unified language, education, and advocacy.
Learn More >Studies showed that upregulation of Nav1.6 increased the neuronal excitability and participated in neuropathic pain in the dorsal root ganglion (DRG). However, the molecular mechanisms underlying Nav1.6 upregulation were not reported yet.
Learn More >Migraine is a debilitating neurological condition that involves the neuropeptide calcitonin gene-related peptide (CGRP). An exciting development is the recent FDA approval of the first in an emerging class of CGRP-targeted drugs designed to prevent migraine. Yet despite this efficacy, there are some fundamental unanswered questions, such as and CGRP works in migraine. Preclinical data suggest that CGRP acts via both peripheral and central mechanisms. The relevance of peripheral sites is highlighted by the clinical efficacy of CGRP-blocking antibodies, even though they do not appreciably cross the blood-brain barrier. The most likely sites of action are within the dura and trigeminal ganglia. Furthermore, it would be foolish to ignore perivascular actions in the dura since CGRP is the most potent vasodilatory peptide. Ultimately, the consequence of blocking CGRP or its receptor is reduced peripheral neural sensitization. Underlying their efficacy is the question of the antibodies have such an excellent safety profile so far. This may be due to the presence of a second CGRP receptor and vesicular release of a large bolus of peptides. Finally, despite the promise of these drugs, there are unmet gaps because they do not work for all patients; so ? We can expect advances on several fronts, including CGRP receptor structures that may help development of centrally-acting antagonists, combinatorial treatments that integrate other therapies, and development of drugs that target other neuropeptides. This is truly an exciting time for CGRP and the migraine field with many more discoveries on the horizon.
Learn More >Neuron-glia interactions contribute to pain initiation and sustainment. Intra-ganglionic (IG) secretion of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) modulates pain transmission through neuron-glia signaling, contributing to various orofacial pain conditions. The present study aimed to investigate the role of satellite glial cells (SGC) in TG in causing cytokine-related orofacial nociception in response to IG administration of CGRP. For that purpose, CGRP alone (10 μL of 10 M), Minocycline (5 μL containing 10 μg) followed by CGRP with one hour gap (Min + CGRP) were administered directly inside the TG in independent experiments. Rats were evaluated for thermal hyperalgesia at 6 and 24 h post-injection using an operant orofacial pain assessment device (OPAD) at three temperatures (37, 45 and 10 °C). Quantitative real-time PCR was performed to evaluate the mRNA expression of IL-1β, IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), sodium channel 1.7 (NaV 1.7, for assessment of neuronal activation) and glial fibrillary acidic protein (GFAP, a marker of glial activation). The cytokines released in culture media from purified glial cells were evaluated using antibody cytokine array. IG CGRP caused heat hyperalgesia between 6⁻24 h (paired- test, < 0.05). Between 1 to 6 h the mRNA and protein expressions of GFAP was increased in parallel with an increase in the mRNA expression of pro-inflammatory cytokines IL-1β and anti-inflammatory cytokine IL-1RA and NaV1.7 (one-way ANOVA followed by Dunnett's post hoc test, < 0.05). To investigate whether glial inhibition is useful to prevent nociception symptoms, Minocycline (glial inhibitor) was administered IG 1 h before CGRP injection. Minocycline reversed CGRP-induced thermal nociception, glial activity, and down-regulated IL-1β and IL-6 cytokines significantly at 6 h (-test, < 0.05). Purified glial cells in culture showed an increase in release of 20 cytokines after stimulation with CGRP. Our findings demonstrate that SGCs in the sensory ganglia contribute to the occurrence of pain via cytokine expression and that glial inhibition can effectively control the development of nociception.
Learn More >Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.
Learn More >Voltage-gated sodium (Nav) channels are targets of disease mutations, toxins, and therapeutic drugs. Despite recent advances, the structural basis of voltage sensing, electromechanical coupling, and toxin modulation remains ill-defined. Protoxin-II (ProTx2) from the Peruvian green velvet tarantula is an inhibitor cystine-knot peptide and selective antagonist of the human Nav1.7 channel. Here, we visualize ProTx2 in complex with voltage-sensor domain II (VSD2) from Nav1.7 using X-ray crystallography and cryoelectron microscopy. Membrane partitioning orients ProTx2 for unfettered access to VSD2, where ProTx2 interrogates distinct features of the Nav1.7 receptor site. ProTx2 positions two basic residues into the extracellular vestibule to antagonize S4 gating-charge movement through an electrostatic mechanism. ProTx2 has trapped activated and deactivated states of VSD2, revealing a remarkable ∼10 Å translation of the S4 helix, providing a structural framework for activation gating in voltage-gated ion channels. Finally, our results deliver key templates to design selective Nav channel antagonists.
Learn More >How do neuropeptides participate in the classic neuroinflammatory sequelae of tissue injury that includes pain, immune cell infiltration, and swelling? In this issue of Neuron, Green et al. (2019) reveal that MrgprB2/MrgprX2 is a mast cell substance-P-specific receptor that critically links neural and immune systems and offers new approaches for neuroinflammatory therapeutics.
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