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Fibromyalgia syndrome (FM) represents a great challenge for clinicians and researchers because the efficacy of currently available treatments is limited. The present study examined the efficacy of Mindfulness-Based Stress Reduction (MBSR) for reducing functional impairment as well as the role of mindfulness-related constructs as mediators of treatment outcomes for people with FM. 225 participants with FM were randomized into three study arms: MBSR plus treatment-as-usual (TAU), FibroQoL (multicomponent intervention for FM) plus TAU, and TAU alone. The primary endpoint was functional impact (measured with the Fibromyalgia Impact Questionnaire Revised), and secondary outcomes included "fibromyalginess", anxiety and depression, pain catastrophising, perceived stress and cognitive dysfunction. The differences in outcomes between groups at post-treatment assessment (primary endpoint) and 12-month follow-up were analyzed using linear mixed-effects models and mediational models through path analyses. MBSR was superior to TAU both at post-treatment (large effect sizes) and at follow-up (medium to large effect sizes), and MBSR was also superior to FibroQoL post-treatment (medium to large effect sizes), but long-term it was only modestly better (significant differences only in pain catastrophising and fibromyalginess). Immediately post-treatment, the NNT for 20% improvement in MBSR versus TAU and FibroQoL was 4.0 (95%CI= 2.1-6.5) and 5.0 (95%CI= 2.7-37.3). An unreliable NNT value of 9 (not computable 95%CI) was found for FibroQoL vs. TAU. Changes produced by MBSR in functional impact were mediated by psychological inflexibility and the mindfulness facet Acting with awareness. These findings are discussed in relation to previous studies of psychological treatments for FM.
Learn More >Delayed onset muscle soreness (DOMS) is characterised by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.
Learn More >We present structures of mouse TRPV3 in temperature-dependent open, closed and intermediate states that suggest two-step activation of TRPV3 by heat. During the strongly temperature-dependent first step, sensitization, the channel pore remains closed while S6 helices undergo α-to-π transitions. During the weakly temperature-dependent second step, channel opening, tight association of the S1-S4 and pore domains is stabilized by changes in the carboxy-terminal and linker domains.
Learn More >The alpha 7 nicotinic acetylcholine receptor, α7 nAChR, plays a central role in regulating inflammatory responses. Previous studies showed that pharmacological inhibitors of α7nAChR have a pro-inflammatory effect, increasing the circulating levels of cytokines such as tumor necrosis factor alpha (TNFα). This study focused on how genetic polymorphisms of the partially duplicated α7nAChR gene (CHRFAM7A), which is highly expressed in peripheral blood cells, contribute to functional outcome after spinal cord injury (SCI). In a cohort of 27 SCI patients and 25 emergency room consented controls (% F/M: 15/85; 24/76, mean ± SE age: 35 ± 1.38 and 35 ± 2.0 respectively), a panel of circulating cytokines, noradrenergic metabolite (normetanephrine [NMN]) levels, and clinical data were available within the first 7 days post-injury (DPI) up to 90 DPI, and were investigated in the acute/subacute (DPI 1-21) and intermediate (DPI 22-90) temporal periods. Cytokine and NMN plasma levels on different DPI were analyzed as a function of CHRFAM7A genotype. TNFα levels, as a representative of some elevated inflammatory mediators, were nearly 3-fold higher in individuals carrying the del2bp variant of the CHRFAM7A gene compared to that in the no deletion genotype (p = 0.001 ANOVA) 3-wks DPI, and 2-fold higher than genotype matched acute/subacute non-SCI injury controls within 7 days DPI. In contrast, NMN levels were initially unchanged, although after three weeks, NMN levels were significantly decreased in SCI individuals carrying the del2bp variant compared to non-carriers (p = 0.011 ANOVA). Numeric pain scores over this same period post-injury were significantly elevated in SCI patients carrying the del2bp variant relative to non-carriers (p = 0.001 ANOVA). Taken together, these data reveal that pro-inflammatory responses associated with CHRFAM7A gene variation may also be associated with differences in pain experience in patients following SCI, at least during the intermediate phase.
Learn More >Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder resulting from germline mutations in the NF1 gene, which encodes neurofibromin. Patients experience a variety of symptoms, but pain in the context of NF1 remains largely under-recognized. Here, we characterize nociceptive signaling and pain behaviors in a miniswine harboring a disruptive NF1 mutation (exon 42 deletion). We present the first characterization of pain-related behaviors in a pig model of NF1, identifying unchanged agitation scores, lower tactile thresholds (allodynia), and decreased response latencies to thermal laser stimulation (hyperalgesia) in NF1 (females only) pigs. Male NF1 pigs with tumors showed reduced sleep quality and increased resting, two health-related quality of life symptoms found to be comorbid in people with NF1 pain. We explore these phenotypes in relationship to suppression of the increased activity of the N-type voltage-gated calcium (CaV2.2) channel by pharmacological antagonism of phosphorylation of a regulatory protein – the collapsin response mediator protein 2 (CRMP2), a known interactor of neurofibromin, and by targeting the interface between the α subunit of CaV2.2 and the accessory β-subunits with small molecules. Our data supports the use of NF1 pigs as a large animal model for studying NF1-associated pain and for understanding the pathophysiology of NF1. Our findings demonstrate the translational potential of two small molecules in reversing ion channel remodeling seen in NF1. Interfering with CaV2.2, a clinically validated target for pain management, might also be a promising therapeutic strategy for NF1-related pain management.
Learn More >mRNA function is meticulously controlled. We provide an overview of the integral role that posttranscriptional controls play in the perception of painful stimuli by sensory neurons. These specialized cells, termed nociceptors, precisely regulate mRNA polarity, translation, and stability. A growing body of evidence has revealed that targeted disruption of mRNAs and RNA-binding proteins robustly diminishes pain-associated behaviors. We propose that the use of multiple independent regulatory paradigms facilitates robust temporal and spatial precision of protein expression in response to a range of pain-promoting stimuli. This article is categorized under: RNA in Disease and Development > RNA in Disease Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability.
Learn More >Given the scarce literature data on chronic post-traumatic pain, we aim to identify early predictors of long-term pain and pain medication use after major trauma.
Learn More >Migraine is a lifelong condition that disproportionately affects women and, if not effectively managed, can lead to significant disability. It is important for clinicians to have a good understanding of the impact of the hormonal fluctuations that occur throughout a female migraineur's life, so that appropriate, stratified therapies can be implemented. In doing so, whether it is migraine onset at menarche in an adolescent young woman, or migraine worsening in a perimenopausal female migraineur, quality of life can be ensured.
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