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A critical component of brain network architecture is a robust hub structure, wherein hub regions facilitate efficient information integration by occupying highly connected and functionally central roles in the network. Across a wide range of neurological disorders, hub brain regions seem to be disrupted, and the character of this disruption can yield insights into the pathophysiology of these disorders. We applied a brain network-based approach to examine hub topology in fibromyalgia, a chronic pain condition with prominent central nervous system involvement. Resting state functional magnetic resonance imaging data from 40 fibromyalgia patients and 46 healthy volunteers, and a small validation cohort of 11 fibromyalgia patients, were analyzed using graph theoretical techniques to model connections between 264 brain regions. In fibromyalgia, the anterior insulae functioned as hubs and were members of the rich club, a highly interconnected nexus of hubs. In fibromyalgia, rich-club membership varied with the intensity of clinical pain: the posterior insula, primary somatosensory, and motor cortices belonged to the rich club only in patients with the highest pain intensity. Furthermore, the eigenvector centrality (a measure of how connected a region is to other highly connected regions) of the posterior insula positively correlated with clinical pain and mediated the relationship between glutamate + glutamine (assessed by proton magnetic resonance spectroscopy) within this structure and the patient's clinical pain report. Together, these findings reveal altered hub topology in fibromyalgia and demonstrate, for the first time to our knowledge, a neurochemical basis for altered hub strength and its relationship to the perception of pain.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Migraine Age of Onset and Association With Ischemic Stroke in Late Life: 20 Years Follow-Up in ARIC.
To evaluate the association between cumulative exposure to migraine and incidence of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.
Learn More >To assess the clinical utility of 5 physical therapy (PT) outcome measures in quantifying functional changes in pediatric lower extremity chronic pain treated at a hospital-based interdisciplinary rehabilitation center.
Learn More >To understand the efficacy of zolmitriptan applied with Adhesive Dermally Applied Microarray (ADAM) in treating types of migraine (those with severe headache pain, the presence of nausea, treatment ≥2 hours after migraine onset, or migraine present upon awakening) that are historically considered to be less responsive to oral medications.
Learn More >Local infiltration analgesia (LIA) is an effective pain management technique following total knee arthroplasty (TKA).
Learn More >The efficacy of preemptive analgesia for prevention of phantom limb pain has been controversial although pain management before amputation is empirically important. The aim of this study was to determine the associated factors with perioperative phantom limb pain.
Learn More >Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) that exerts analgesic and anti-inflammatory actions. The transient receptor potential ankyrin 1 (TRPA1) channel, expressed primarily in nociceptors, mediates the action of proalgesic and inflammatory agents. Ibuprofen metabolism yields the reactive compound, ibuprofen-acyl glucuronide, which, like other TRPA1 ligands, covalently interacts with macromolecules. To explore whether ibuprofen-acyl glucuronide contributes to the ibuprofen analgesic and anti-inflammatory actions by targeting TRPA1, we used in vitro tools (TRPA1-expressing human and rodent cells) and in vivo mouse models of inflammatory pain. Ibuprofen-acyl glucuronide, but not ibuprofen, inhibited calcium responses evoked by reactive TRPA1 agonists, including allyl isothiocyanate (AITC), in cells expressing the recombinant and native human channel and in cultured rat primary sensory neurons. Responses by the non-reactive agonist, menthol, in a mutant human TRPA1 lacking key cysteine-lysine residues, were not affected. In addition, molecular modeling studies evaluating the covalent interaction of ibuprofen-acyl glucuronide with TRPA1 suggested the key cysteine residue C621 as a probable alkylation site for the ligand. Local administration of ibuprofen-acyl glucuronide, but not ibuprofen, in the mouse hind paw attenuated nociception by AITC and other TRPA1 agonists and the early nociceptive response (phase I) to formalin. Systemic ibuprofen-acyl glucuronide and ibuprofen, but not indomethacin, reduced phase I of the formalin response. Carrageenan-evoked allodynia in mice was reduced by local ibuprofen-acyl glucuronide, but not by ibuprofen, whereas both drugs attenuated PGE levels. Ibuprofen-acyl glucuronide, but not ibuprofen, inhibited the release of IL-8 evoked by AITC from cultured bronchial epithelial cells. The reactive ibuprofen metabolite selectively antagonizes TRPA1, suggesting that this novel action of ibuprofen-acyl glucuronide might contribute to the analgesic and anti-inflammatory activities of the parent drug.
Learn More >A study published in PAIN in 2010 showed remarkable effects of intradiscal methylene blue (MB) injections compared with placebo on pain intensity in patients with chronic discogenic low back pain (CD-LBP). Both groups received lidocaine hydrochloride injections for pain associated with the procedure. We replicated the design of the previously published study and performed a multicenter, double-blind, randomized, placebo-controlled trial to assess whether the extraordinary effects of MB on pain intensity could be confirmed. The primary outcomes were treatment success defined as at least 30% reduction in pain intensity and the Patients' Global Impression of Change 6 months after the intervention. We included 84 patients with CD-LBP of which 14 (35%) in the MB plus lidocaine group showed treatment success compared with 11 (26.8%) in the control group who received placebo plus lidocaine (P = 0.426). Twenty-seven percent of all participants treated with MB stated that their overall health improved much or very much (Patients' Global Impression of Change), vs 25.6% in the placebo group (P = 0.958). We were unable to confirm that intradiscal MB injections are better capable of significantly reducing pain in patients with CD-LBP 6 months after treatment compared with placebo. We observed that over one-quarter of patients receiving only lidocaine injections reported treatment success, which is in contrast with the previously published study. Our results do not support the recommendation of using intradiscal MB injections for patients with CD-LBP.
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