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Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial.

Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments.

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Examining the adjustment patterns of adults with multiple chronic pain conditions and multiple pain sites: More pain, no gain.

The present study examined how multiple chronic pain conditions and pain sites are associated with socio-demographics, chronic pain adjustment profiles, and emotional distress. A total of 2407 individuals who reported at least six months of having consistent pain severity, pain interference, and/or emotional burden due to pain were recruited through random digit dialing across the United States. Participants' chronic pain adjustment profiles (i.e., pain intensity, pain interference, emotional burden, pain catastrophizing, pain coping, pain attitudes, and social resources) were assessed. Anxiety and depressive symptoms were also measured using a subsample of 181 participants who provided three-month follow-up data. More than 60% of individuals with chronic pain reported having multiple pain conditions. Middle-aged single women with fibromyalgia, disability and of low socioeconomic status reported a greater number of pain conditions and pain sites. Structural equation modeling revealed that a higher number of pain conditions and sites was associated with more dysfunctional chronic pain adjustment profiles. The subsample analyses showed that reporting a greater number of pain conditions predicted a higher level of depression and anxiety three months later, controlling for pain-related anxiety and depressive symptoms, pain severity and interference at baseline. Having multiple pain conditions and sites may represent a psychosocial barrier to successful adjustment to chronic pain. Perspectives: This article argues for the importance of assessing the number of co-occurring chronic pain conditions and bodily areas that are affected by pain in both pain research and clinical settings. Measuring and incorporating such information could potentially enhance our nascent understanding of the adjustment processes of chronic pain.

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Injustice Appraisal but not Pain Catastrophizing Mediates the Relationship Between Perceived Ethnic Discrimination and Depression and Disability in Low Back Pain.

Despite growing evidence of significant racial disparities in the experience and treatment of chronic pain, the mechanisms by which these disparities manifest have remained relatively understudied. The current study examined the relationship between past experiences of racial discrimination and pain-related outcomes (self-rated disability and depressive symptomatology), and tested the potential mediating roles of pain catastrophizing and perceived injustice related to pain. Analyses consisted of cross-sectional path modeling in a multiracial sample of 137 individuals with chronic low back pain (Hispanics N=43; Blacks N=43; Whites N=51). Results indicated a positive relationship between prior discriminatory experiences and severity of disability and depressive symptoms. In mediation analyses, pain-related appraisals of injustice, but not pain catastrophizing, were found to mediate these relationships. Notably, the association between discrimination history and perceived injustice was significantly stronger in Black and Hispanic participants and was not statistically significant in White participants. The findings suggest that race-based discriminatory experiences may contribute to racial disparities in pain outcomes and highlight the specificity of pain-related, injustice-related appraisals as a mechanism by which these experiences may impair physical and psychosocial function. Future research is needed to investigate temporal and causal mechanisms suggested by the model through longitudinal and clinical intervention studies. PERSPECTIVE: More frequent prior experiences of racial discrimination are associated with greater depressive symptomatology and pain-related disability in individuals with chronic low back pain. These associations are explained by the degree of injustice perception related to pain, but not pain catastrophizing, and were stronger among Black and Hispanic participants.

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Trial of Galcanezumab in Prevention of Episodic Cluster Headache.

Episodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.

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Sex Differences in Interleukin-6 Responses Over Time Following Laboratory Pain Testing Among Patients With Knee Osteoarthritis.

Epidemiological studies suggest that women are not only at a higher risk for developing knee osteoarthritis (KOA), but also report greater symptom severity compared to men. One potential underlying mechanism of these sex differences may be exaggerated inflammatory responses to pain among women compared to men. The present study examined sex differences in interleukin-6 (IL-6) response over time following experimental pain testing. We hypothesized that women, when compared to men, would show greater IL-6 reactivity when exposed to acute pain in a human laboratory setting. Eighty-four participants (36 men and 48 women) with KOA scheduled for total knee arthroplasty underwent a quantitative sensory testing (QST) battery. A total of seven IL-6 measurements were taken, twice at baseline, once immediately after QST, and every 30 minutes up to 2 hours after QST. Consistent with our hypothesis, women, when compared to men, showed accelerated increases in IL-6 levels following laboratory-evoked pain, even after controlling for body mass index, marital status, clinical pain, evoked pain sensitivity, and situational pain catastrophizing. Given that KOA is a chronic condition, and individuals with KOA frequently experience pain, these sex differences in IL-6 reactivity may contribute to the maintenance and/or exacerbation of KOA symptoms. PERSPECTIVES: The present study demonstrates that women, when compared to men, exhibit greater IL-6 reactivity after exposure to laboratory-evoked pain. Such sex differences may explain the mechanisms underlying women's higher chronic pain risk and pain perception, as well as provide further insight in developing personalized pain interventions.

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Tapentadol prolonged release for managing moderate to severe chronic neck pain with or without a neuropathic component.

Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition. We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL). Observational, retrospective study. Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment. The primary endpoint was a ≥30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL. Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily. At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% (n = 35; 95% confidence interval [CI]: 55-82%) of patients with a neuropathic pain component and in 69% (n = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion (P < 0.01), with no difference between the two groups. Interference of pain with sleep and QoL also improved. The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL.

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The Relationship between Clinical and Quantitative Measures of Pain Sensitization in Knee Osteoarthritis.

Pain sensitization in knee osteoarthritis is associated with greater symptom severity and poorer clinical outcomes. Measures which identify pain sensitization and are accessible to use in clinical practice have been suggested to enable more targeted treatments. This merits further investigation. This study examines the relationship between Quantitative Sensory Testing (QST) and clinical measures of pain sensitization in people with knee osteoarthritis.

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Calcium-inducible MAPK/AP-1 signaling drives semaphorin 3A expression in normal human epidermal keratinocytes.

Epidermal keratinocytes express semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression transiently increased in calcium-stimulated NHEKs, but markedly decreased in terminally differentiated NHEKs. Sema3A mRNA mainly localized in the stratum basale and stratum suprabasale of the epidermis. The 5'-flanking region of the Sema3A gene was cloned, and a critical region for Sema3A promoter activity within -134 bp of the start codon was identified. Transcription factor binding sites, including that for activator protein (AP)-1, were found in this region. Sema3A expression was increased by the co-overexpression of JunB and Fra-2 in the presence of 0.1 or 1.4 mM calcium. The calcium-mediated transient up-regulation of Sema3A expression was significantly suppressed by mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] (MEK) 1/2 or AP-1 inhibitors. These results demonstrate that the calcium-mediated transient up-regulation of Sema3A in NHEKs is involved in the MEK/ERK and AP-1 signaling axis. Therefore, Sema3A mRNA may be expressed in the lower epidermis under controlled conditions by calcium via the MAPK-AP1 axis.

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Associations between migraine attacks and nightly sleep characteristics among adults with episodic migraine: a prospective cohort study.

Given the unknown immediate impact of migraine on nighttime sleep, we prospectively examined whether migraine headaches were associated with subsequent shorter sleep duration, higher fragmentation and poorer quality in a cohort of 98 adults with episodic migraine.

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Musculoskeletal pain in 6-year-old children: the Generation R Study.

Musculoskeletal (MSK) pain is frequently reported among adolescents and children and a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6-years of age (N=6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain and behavioral problems were extracted from questionnaires. The BMI SD score was calculated from objectively measured weight and height. A three-month prevalence of 10.0% was found for MSK pain in children, of which one third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status (SES) reported MSK pain more frequent compared to other pain and no pain. While no associations were found between MSK pain and children's BMI and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (OR 5.10, 95% CI 3.25 to 7.98) and behavioral problems (OR 2.10, 95% CI 1.19 to 3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral problems are independently associated with MSK pain in the studied population.

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