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Health-related quality of life and economic burden of chronic pruritus.

Chronic pruritus has considerable implications for quality of life (QoL). However, its impact on health-related QoL and economic burden is not fully characterized. We administered a cross-sectional survey of 132 patients with chronic pruritus using the Health Utilities Index Mark 3 (HUI3) instrument. Normative data from healthy adults (n=4,187) were obtained from the Joint Canada/U.S. Survey of Health. Quality-adjusted life-year (QALY) loss and economic costs were estimated based on HUI3 scores of chronic pruritus patients vs. controls. Patients with chronic pruritus had lower overall health performance compared to the control (0.56±0.03 vs. 0.86±0.003, p<0.001). In multivariable regression, chronic pruritus was associated with worse overall health performance (coefficient -0.30, 95% CI [-0.33 to -0.27]), most accentuated in the domains of pain (coefficient -0.24, [-0.28 to -0.21]) and emotion (coefficient -0.11, [-0.13 to -0.10]). The reduced HUI3 score correlated to 5.5 average lifetime QALYs lost per patient. Using conservative estimates for willingness-to-pay, the QALY loss translated to an individual lifetime economic burden of $274,921 and a societal burden of $88.8 billion. Chronic pruritus is associated with significant QoL impairment. The economic burden of chronic pruritus highlights the necessity of further research into management options.

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Pain Catastrophizing Does Not Predict Spinal Cord Stimulation Outcomes: A Cohort Study of 259 Patients With Long-Term Follow-Up.

Spinal cord stimulation (SCS) is an important treatment modality used to treat chronic neuropathic pain. However, reported success rates of 26%-70% entail an increased focus on patient selection. An area of core interest is psychological evaluation, often using scales such as the Pain Catastrophizing Scale (PCS). The aim of this study was to assess the relation between baseline PCS scores obtained before implantation and SCS outcomes defined as (1) Rating on Patients' Global Impression of Change scale (PGIC), (2) Pain relief on the Numeric Rating Scale (NRS), (3) Cessation of pain medication, and (4) Risk of permanent explantation.

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Preclinical studies to dissect the neural mechanism for the comorbidity of migraine and temporomandibular disorders (TMD): the role of CGRP.

Temporomandibular disorders (TMD) and migraine can be co-morbid. This can be a significant factor in exacerbating and increasing the prevalence of migraine-like symptoms. However, the underlying putative mechanisms involved are not known. Our objective was to dissect these neural mechanisms, and the role of calcitonin gene-related peptide (CGRP) as a key modulator, in this co-morbidity.

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Role of peripheral sensory neuron mu-opioid receptors in nociceptive, inflammatory, and neuropathic pain.

The role of peripheral mu-opioid receptors (MOPs) in chronic pain conditions is not well understood. Here, we used a combination of mouse genetics, behavioral assays, and pharmacologic interventions to investigate the contribution of primary afferent MOPs to nociceptive, inflammatory, and neuropathic pain, as well as to opioid analgesia.

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Haemodynamic activity characterization of resting state networks by fractal analysis and thalamocortical morphofunctional integrity in chronic migraine.

Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC).

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Impaired effective functional connectivity of the sensorimotor network in interictal episodic migraineurs without aura.

Resting-state functional magnetic resonance imaging (Rs-fMRI) has confirmed sensorimotor network (SMN) dysfunction in migraine without aura (MwoA). However, the underlying mechanisms of SMN effective functional connectivity in MwoA remain unclear. We aimed to explore the association between clinical characteristics and effective functional connectivity in SMN, in interictal patients who have MwoA.

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Introducing the National Headache Fellowship Opportunities Website.

To build a national Headache Medicine fellowship opportunities website that promotes a unified application timeline and a more transparent application process.

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Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors.

Morphine promotes neuroinflammation after NOD-like receptor protein 3 (NLRP3) oligomerization in glial cells, but the capacity of other opioids to induce neuroinflammation and its relationship to the development of analgesic tolerance is unknown. We studied the effects of morphine and fentanyl on NLRP3 inflammasome activation in glial and neuronal cells in the dorsal raphe nucleus (DRN), a region involved in pain regulation. Male Wistar rats received i.p. injections of morphine (10 mg/kg) or fentanyl (0.1 mg/kg) 3 × daily for 7 days and were tested for nociception. Two hours after the last (19th) administration, we analyzed NLRP3 oligomerization, caspase-1 activation and gasdermin D-N (GSDMD-N) expression in microglia (CD11b positive cells), astrocytes (GFAP-positive cells) and neurons (NeuN-positive cells). Tolerance developed to both opioids, but only fentanyl produced hyperalgesia. Morphine and fentanyl activated NLRP3 inflammasome in astrocytes and serotonergic (TPH-2-positive) neurons, but fentanyl effects were more pronounced. Both opioids increased GFAP and CD11b immunoreactivity, caspase-1 and GSDMD activation, indicating pyroptotic cell death. The opioid receptor antagonist (-)-naloxone, but not the TLR4 receptor antagonist (+)-naloxone, prevented microglia activation and NLRP3 oligomerization. Only (+)-naloxone prevented astrocytes' activation. The anti-inflammatory agent minocycline and the NLRP3 inhibitor MCC950 delayed tolerance to morphine and fentanyl antinociception and prevented fentanyl-induced hyperalgesia. MCC950 also prevented opioid-induced NLRP3 oligomerization. In conclusion, morphine and fentanyl differentially induce cell-specific activation of NLRP3 inflammasome and pyroptosis in the DRN through TLR4 receptors in astrocytes and through opioid receptors in neurons, indicating that neuroinflammation is involved in opioid-induced analgesia and fentanyl-induced hyperalgesia after repeated administrations.

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Posttraumatic growth and depreciation in people with chronic pain: A profile analysis.

Chronic pain can disrupt everyday life and shatter beliefs about the world. Shattered beliefs may be rebuilt, either positively or negatively, leading to posttraumatic growth (PTG) or posttraumatic depreciation (PTD). According to a transdiagnostic emotion regulation perspective, these phenomena are associated with coping strategies and emotions related to the body, self, others, and the world. Because PTG and PTD can coexist, this study aims to compare different profiles of rebuilt beliefs based on emotions, emotion regulation, and psychopathology.

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Real-World Patient Experience With Erenumab for the Preventive Treatment of Migraine.

Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post-market observations are available to validate these findings in a real-world tertiary headache clinic population with complex comorbidities and refractory migraine.

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