The journal of pain : official journal of the American Pain Society
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Observational Study
Dysregulation in sphingolipid signaling pathways is associated with symptoms and functional connectivity of pain processing brain regions in provoked vestibulodynia.
Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. ⋯ This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker that could provide new targets for therapeutic intervention.
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Musculoskeletal pain is an aversive experience that exists within a variety of conditions and can result in significant impairment for individuals. Gaining greater understanding of the factors related to pain vulnerability and resilience to musculoskeletal pain may help target at-risk individuals for early intervention. This analysis builds on our previous work identifying regions where greater gray matter density was associated with lower pain following standardized, exercise induced musculoskeletal injury. ⋯ Results suggest resilience to clinically relevant pain is associated with aspects of regional and network neural coherence. Investigations of pain modulatory capacity that integrate multimodal neuroimaging metrics are called for. PERSPECTIVE: Our results provide key support for the role of structural and functional coherence in regional and network connectivity in adaptive pain response and represent an important step in clarifying neural mechanisms of resilience to clinically relevant pain.
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Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache, and pain conditions. ⋯ PERSPECTIVE: This study provides insights into the underlying mechanisms of chronic pain. Higher levels of GABA+ in the PCG may reflect an underlying mechanism of chronic headache and pain conditions. This knowledge may help improve patient outcomes through developing treatments that specifically address this aberrant brain neurochemistry.
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Neuropathic pain is a common disability produced by enhanced neuronal excitability after nervous system injury. The pathophysiological changes that underlie the generation and maintenance of neuropathic pain require modifications of transcriptional programs. In particular, there is an induction of pro-inflammatory neuromodulators levels, and changes in the expression of ion channels and other factors intervening in the determination of the membrane potential in neuronal cells. ⋯ PERSPECTIVE: Neuropathic pain is a common disability produced by enhanced neuronal excitability after nervous system injury. The underlying pathophysiological changes require modifications of transcriptional programs. This study notes that inhibition of BET proteins is a promising therapy for reducing neuropathic pain after neural injury.