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Because nitric oxide could play an important role in the pathogenesis of migraine (suggested by experimental, neuropathological, biochemical, and pharmacological data), and a recent meta-analysis showed an association between the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for migraine in Caucasians, we attempted to replicate the possible association between this SNP and the and the risk for migraine in the Caucasian Spanish population. The frequencies for the NOS3 rs2070744 genotypes and allelic variants were assessed in 283 migraine patients and 287 healthy controls with a TaqMan-based qPCR Assay. The putative influence on genotype frequency of age at onset of migraine attacks, gender, family history of migraine, absence or presence of aura, and triggering of migraine attacks by ethanol, were also analyzed. The frequencies of NOS3 rs2070744 genotypes and allelic variants were not associated with the risk for migraine (OR [95%] CI for the minor allele = 0.91 [0.72-1.15]) and were not influenced by age at onset of migraine, gender, presence of aura, or triggering of migraine attacks by ethanol. NOS3 rs2070744CC genotypes were significantly more frequent in patients with a family history of migraine. NOS3 rs2070744 SNP is not associated with the risk for migraine in Caucasian Spanish people although it might be related to family history.
Learn More >Although degenerative disc disease (DDD) and related low back pain (LBP) are growing public health problems, the underlying disease mechanisms remain unclear. An increase in the vascular endothelial growth factor (VEGF) levels in DDD has been reported. This study aimed to examine the role of VEGF receptors (VEGFRs) in DDD, using a mouse model of DDD. Progressive DDD was induced by anterior stabbing of lumbar intervertebral discs in wild type (WT) and VEGFR-1 tyrosine-kinase deficient mice (vegfr-1 ). Pain assessments were performed weekly for 12 weeks. Histological and immunohistochemical assessments were made for discs, dorsal root ganglions, and spinal cord. Both vegfr-1 and WT mice presented with similar pathological changes in discs with an increased expression of inflammatory cytokines and matrix-degrading enzymes. Despite the similar pathological patterns, vegfr-1 mice showed insensitivity to pain compared with WT mice. This insensitivity to discogenic pain was related to lower levels of pain factors in the discs and peripheral sensory neurons and lower spinal glial activation in the vegfr-1 / mice than in the WT mice. Exogenous stimulation of bovine disc cells with VEGF increased inflammatory and cartilage degrading enzyme. Silencing vegfr-1 by small-interfering-RNA decreased VEGF-induced expression of pain markers, while silencing vegfr-2 decreased VEGF-induced expression of inflammatory and metabolic markers without changing pain markers. This suggests the involvement of VEGFR-1 signaling specifically in pain transmission. Collectively, our results indicate that the VEGF signaling is involved in DDD. Particularly, VEGFR-1 is critical for discogenic LBP transmission independent of the degree of disc pathology.
Learn More >The purpose of this study is to determine the association between presence of chronic pain and school functioning among school aged children (6-17▒y) using the most recent United States national data.
Learn More >Analgesic treatments that aim to eliminate pain display marginal success in relieving chronic pain and may increase pain vulnerability. Repeated exposure to pain may result in increased pain modulation via engagement of anti-nociceptive brain regions. It was hypothesized that repeated exposure to delayed onset muscle soreness (DOMS) would result in increased pain modulatory capacity (PMC) via functional neural adaptation. 23 healthy participants completed Baseline and Follow Up resting-state fMRI and quantitative sensory testing (QST) visits 40 days apart. Participants were randomized to two groups: A Repeated DOMS Group (RD Group) that received four, weekly DOMS inductions and a Control Group that received one baseline induction. Daily pain ratings were collected for seven days post-induction, as were quantitative sensory testing (QST) metrics at baseline and Follow Up. Regional functional connectivity (FC) was estimated among areas involved in pain modulation. Seed and network FC was estimated among areas involved in pain modulation and sensory processing. Changes in FC were compared between groups. The RD Group displayed significant reductions in post-DOMS pain ratings and significant changes in thermal QST measures. RD Group participants displayed greater adaptation in nucleus accumbens-medial prefrontal cortex (NAc-mPFC) FC and in sensorimotor network (SMN) connectivity with the dorsomedial, ventromedial, and rostromedial prefrontal cortices. Changes in SMN-PFC connectivity correlated with reductions in post-DOMS affective distress. Results suggest that repeated exposure to clinically-relevant pain results in adaptations among brain regions involved in pain modulation. Repeated exposure to clinically-relevant pain may serve as a mechanism to increase PMC via inhibition of emotional valuation of painful stimuli.
Learn More >The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine-induced myalgia model (RIM) lowers pain thresholds and produces depressive-like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and EMG activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on 3 consecutive days to achieve the RIM. Post-reserpine recordings were taken on alternate days for 21 days. Reserpine induced changes in the sleep architecture with more transitions between states, and a different pattern between the administration period and post-reserpine weeks. Administration days were characterized by a larger amount of REM sleep with dominant theta waves without atonia. Following the reserpinization, theta oscillations were always more fragmented and with lower frequency. On the post-reserpine days, sleep was dominated by slow-wave sleep with fast intrusions and reduced hierarchical coupling with spindles and ripples. Simultaneous electromyography recordings also showed muscle twitches during sleep and the dissociation of theta activity and muscle atonia. Abnormally high slow waves, alpha/delta intrusions, frequent transitions and muscle twitches are common traits in fibromyalgia. Therefore, our analyses support the validity of the reserpine-induced myalgia model to study sleep disorders in fibromyalgia, and provide new insights into the research of oscillographic biomarkers. This article is protected by copyright. All rights reserved.
Learn More >We conducted focus groups in people who had participated in mobile health (mHealth) studies of behavioral interventions for migraine to better understand: (a) Participant experience in the recruitment/enrollment process; (b) participant experience during the studies themselves; (c) ideas for improving participant experience for future studies.
Learn More >To investigate whether meteorological factors (temperature, barometric pressure, relative humidity, ultraviolet index [UVI], and seasons) trigger flares in male and female urologic chronic pelvic pain patients.
Learn More >Chronic low back pain (cLBP) is the leading cause of disability, with a significant societal cost. It disproportionately affects Non-Hispanic Blacks and individuals of lower socioeconomic status (SES). The biopsychosocial framework has been used to study and manage cLBP, yet disparities persist.
Learn More >To prioritize outcome domains sensitive to the needs of the various stakeholders involved in rehabilitation programs designed for youth with pain-related disability using the International Classification of Function Child and Youth version.
Learn More >The transient receptor potential melastatin type 8 (TRPM8) receptor channel is expressed in primary afferent neurons where it is the main transducer of innocuous cold temperatures and also in a variety of tumors, where it is involved in progression and metastasis. Modulation of this channel by intracellular signaling pathways has therefore important clinical implications. We investigated the modulation of recombinant and natively expressed TRPM8 by the Src kinase, which is known to be involved in cancer pathophysiology and inflammation. Human TRPM8 expressed in HEK293T cells is constitutively tyrosine phosphorylated by Src which is expressed either heterologously or endogenously. Src action on TRPM8 potentiates its activity, as treatment with PP2, a selective Src kinase inhibitor, reduces both TRPM8 tyrosine phosphorylation and cold-induced channel activation. RNA interference directed against the Src kinase diminished the extent of PP2-induced functional downregulation of TRPM8, confirming that PP2 acts mainly through Src inhibition. Finally, the effect of PP2 on TRPM8 cold activation was reproduced in cultured rat dorsal root ganglion neurons, and this action was antagonized by the protein tyrosine phosphatase inhibitor pervanadate, confirming that TRPM8 activity is sensitive to the cellular balance between tyrosine kinases and phosphatases. This positive modulation of TRPM8 by Src kinase may be relevant for inflammatory pain and cancer signaling.
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