Pain
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Chronic pain is a prevalent disease with increasing clinical challenges. Genome-wide association studies in chronic pain patients have identified hundreds of common pathogenic variants, yet they only explained a portion of individual variance of chronic pain. With the advances in next-generation sequencing technologies, it is now feasible to conduct rarer variants studies in large-scale databases. ⋯ These 2 rare variants were then tested for replication in 3 other biobanks, and the strongest evidence was found for rs28364172 as an individual contributor. Transcriptional analyses of Slc13a1 in rodents showed substantial regulation of its expression in the dorsal root ganglia and the sciatic nerve in neuropathic pain assays. Our results stress the importance of the SLC13A1 gene in sulfate homeostasis in the nervous system and its critical role in preventing pain states, thus suggesting new therapeutic approaches for treating chronic pain in a personalized manner, especially in people with mutations in the SLC13A1 gene.
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Debilitating pain affects the lives of patients with sickle cell disease (SCD). Current pain treatment for patients with SCD fail to completely resolve acute or chronic SCD pain. Previous research indicates that the cation channel transient receptor potential vanilloid type 4 (TRPV4) mediates peripheral hypersensitivity in various inflammatory and neuropathic pain conditions that may share similar pathophysiology with SCD, but this channel's role in chronic SCD pain remains unknown. ⋯ TRPV4 blockade also reduced the mechanical sensitivity of small, but not large, dorsal root ganglia neurons from mice with SCD. Furthermore, keratinocytes from mice with SCD showed sensitized TRPV4-dependent calcium responses. These results shed new light on the role of TRPV4 in SCD chronic pain and are the first to suggest a role for epidermal keratinocytes in the heightened sensitivity observed in SCD.
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To elucidate the physiological, cellular, and molecular mechanisms responsible for initiating and sustaining ocular neuropathic pain, we created a blue-light-exposure model in C57BL/6 mice. Mice were exposed to 12 h of blue or white light followed by 12 h of darkness. Before blue light exposure, baseline tear secretion, stability, and ocular hyperalgesia were assessed by measuring hyper- or hypo-osmotic solution-induced eye wiping, wind-induced eye closing, and cold-induced eye blinking. ⋯ TRPV1 and substance P expression was increased, whereas CGRP expression deceased at the mRNA level in isolated corneal projecting neurons. Hence, our blue-light exposure B6 mouse model for assessing tearing and ocular hyperalgesia is useful for studying ocular pain and its underlying mechanisms. Blue-light-induced alterations in tearing and ocular hyperalgesia may be related to the elevated expression of TRPV1, SP, and/or the suppressed expression of CGRP at the ocular surface.
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Meta Analysis
Stress biomarkers in individuals with fibromyalgia syndrome: a systematic review with meta-analysis.
Evidence suggests an involvement of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in the development and maintenance of fibromyalgia syndrome (FMS). However, studies on the stress response via the HPA-axis in individuals with FMS show conflicting results. To better understand the relationship between FMS and HPA-axis dysregulation, we (1) systematically summarized the current level of evidence on HPA biomarkers in individuals with FMS compared with individuals without and (2) evaluated whether FMS is associated with a specific pattern of HPA dysregulation. ⋯ However, heterogeneity of data was high with significant evidence for publication bias. Overall, the data are compatible with association of FMS with adrenocortical hypofunction in the presence of increased sympathetic tone. However, the data are partially contradictory, so it must be assumed that the data are highly dependent on the respective study designs, patient samples, and analytical methods and do not necessarily demonstrate an abnormal HPA-axis function in FMS.