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Alterations in Functional Connectivity During Different Phases of the Triggered Migraine Attack.

To understand the changes in functional connectivity between brain areas of potential importance in migraine during different phases of the attack.

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Pain centrality mediates pain self-efficacy and symptom severity among individuals reporting chronic pain.

Chronic pain is consistently associated with the presence of mental health disorders. Although previous research has shown relations between low levels of self-efficacy with chronic pain severity as well as comorbid mental health symptoms, the link between self-efficacy and mental health symptoms in chronic pain is not well understood. This study examined whether pain centrality, the extent to which pain is viewed as central to self-identity, may underlie these associations. Individuals with a diagnosis of chronic pain (N = 89) recruited through MTurkcompleted self-report measures including demographics, self-efficacy, pain centrality, pain severity, depression, and anxiety. Pain severity was associated with higher levels of pain centrality, depression, anxiety, and lower levels of self-efficacy. Path analysis demonstrated pain centrality significantly mediated the relationship between self-efficacy and pain severity, depression, and anxiety. Future studies would benefit from testing whether modifying pain centrality beliefs shift perceptions of control as well as pain and psychological outcomes.

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Voltage-dependent modulation of TRPA1 currents by diphenhydramine.

Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor potential type A1 (TRPA1) channel is known to play roles in both acute and chronic itch and pain, whether DPH affects the activities of TRPA1 remains unclear. Using whole-cell patch clamp recordings, we demonstrated that DPH modulates the voltage-dependence of TRPA1. When co-applied with a TRPA1 agonist, DPH significantly enhanced the inward currents while suppressing the outward currents of TRPA1, converting the channel from outwardly rectifying to inwardly rectifying. This effect of DPH occurred no matter TRPA1 was activated by an electrophilic or non-electrophilic agonist and for both mouse and human TRPA1. The modulation of TRPA1 by DPH was maintained in the L906C mutant, which by itself also causes inward rectification of TRPA1, indicating that additional acting sites are present for the modulation of TRPA1 currents by DPH. Our recordings also revealed that DPH partially blocked capsaicin evoked TRPV1 currents. These data suggest that DPH may exert its therapeutic effects on itch and pain, through modulation of TRPA1 in a voltage-dependent fashion.

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Development and Psychometric Evaluation of the PROMIS® Pediatric Pain Intensity Measure in Children and Adolescents with Chronic Pain.

The goal of the current study was to enhance the measurement of the pediatric chronic pain experience through a methodologically rigorous approach. This paper outlines the development and initial validation of a pain intensity measure for pediatric patients with chronic pain using PROMIS® methodology. Measure development incorporated feedback from children with painful conditions. Based on input from pediatric participants and content experts, four candidate items assessing pain intensity were included for large scale testing. Children completed self-report items pertaining to their pain experience that were developed as part of a larger pool of new candidate PROMIS® pediatric pain domain items as well as measures of pain interference, depressive symptoms, fatigue, pain behavior, pain intensity, and pain catastrophizing. The final sample for the large scale testing included N = 442 pediatric patients between the ages 8 to 18 years (Mean age = 13.54, SD = 2.78; 71.27% female) experiencing chronic pain. Psychometric analysis resulted in a final measure that included three items with evidence of reliability (Cronbach alpha = 0.82) and convergent validity. The Likert format of the response options may be preferable to the traditional numeric rating scale for use in pediatric populations who experience chronic pain based on patients' feedback, which was directly utilized in designing the scale. Further, the inclusion of fewer and clinically meaningful response options should reduce ambiguity for young respondents. Perspective: We have developed and evaluated a clinically sensitive and psychometrically precise 3-item pain intensity measure with Likert-type responses for self-report use among children and adolescents ages 8-18 with chronic pain. Development of the item content and response options included input from children and adolescents with chronic pain. The development of pain intensity items with pediatric appropriate language, and labeled, fewer response options to yield maximal clinically meaningful information improves the precision of pain intensity measurement in children.

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Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain – a double blind randomized control cross-over trial.

Binaural Beats (BB) consist of two artificial acoustic stimuli with different frequency, presented simultaneously but independently to each ear. The human brain perceives and synchronizes to this frequency difference (entrainment).

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The Relationship between Education and Pain among Adults Aged 30-49 in the United States.

Pain is a major health problem among US adults. Surprisingly little, however, is known about educational disparities in pain, especially among the nonelderly. In this study, we analyze disparities in pain across levels of educational attainment. Using data from the 2010-2017 National Health Interview Survey among adults aged 30-49 (N=74,051), we estimate logistic regression models of pain prevalence using a dichotomous summary pain index and its five constituent pain sites (low back, joint, neck, headache/migraine, and facial/jaw). We find a significant and steep pain gradient: greater levels of educational attainment are associated with less pain, with two important exceptions. First, adults with a high-school equivalency diploma (GED) and those with 'some college' have significantly higher pain levels than high school graduates despite having an equivalent or higher attainment, respectively. Second, the education-pain gradient is absent for Hispanic adults. After taking into account important covariates including employment, economic resources, health behaviors, physical health conditions, and psychological wellbeing, educational disparities in pain are no longer statistically significant except for the GED and 'some college' categories, which still show significantly higher pain levels than high school graduates. We thus document the overall education-pain gradient in most younger US adult populations, and identify groups where pain is higher than expected (certain educational categories) or lower than expected (e.g., less-educated Hispanics). Understanding the causes of these anomalous findings could clarify factors shaping pain prevalence and disparities therein. PERSPECTIVE Over 50% of US adults age 30-49 report pain. Overall, more educated Americans report substantially less pain than the less educated. However, adults with a GED and 'some college' report more pain than other groups. Understanding the causes could help illuminate the mechanisms through which social factors influence pain.

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DNA methylation and BDNF expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia.

Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

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Altered resting-state functional connectivity between subregions in the thalamus and cortex in migraine without aura.

Migraine is a complex and disabling neurological disorder, and the exact neurological mechanisms remain unclear. Thalamus is considered the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes.

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A dietary fatty acid counteracts neuronal mechanical sensitization.

PIEZO2 is the essential transduction channel for touch discrimination, vibration, and proprioception. Mice and humans lacking Piezo2 experience severe mechanosensory and proprioceptive deficits and fail to develop tactile allodynia. Bradykinin, a proalgesic agent released during inflammation, potentiates PIEZO2 activity. Molecules that decrease PIEZO2 function could reduce heightened touch responses during inflammation. Here, we find that the dietary fatty acid margaric acid (MA) decreases PIEZO2 function in a dose-dependent manner. Chimera analyses demonstrate that the PIEZO2 beam is a key region tuning MA-mediated channel inhibition. MA reduces neuronal action potential firing elicited by mechanical stimuli in mice and rat neurons and counteracts PIEZO2 sensitization by bradykinin. Finally, we demonstrate that this saturated fatty acid decreases PIEZO2 currents in touch neurons derived from human induced pluripotent stem cells. Our findings report on a natural product that inhibits PIEZO2 function and counteracts neuronal mechanical sensitization and reveal a key region for channel inhibition.

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Trends in gabapentinoid prescribing, co-prescribing of opioids and benzodiazepines, and associated deaths in Scotland.

Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of ∼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs.

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