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Mounting studies pay attention to the functional roles of long non-coding RNAs (lncRNAs) in many human diseases including neuropathic pain. LncRNA MALAT1 has been indicated to serve as a critical mediator in neuropathic pain with unclear mechanisms. The present study aims to explore the functional roles of MALAT1 in neuropathic pain progression and the related mechanisms. Bilateral sciatic nerves were ligated to induce chronic constriction injury (CCI) in order to establish the neuropathic pain rat model followed by behavioral tests, RT-qPCR, Western blotting, and ELISA. Dual luciferase activity assay was performed to determine the binding effect between MALAT1 or HMGB1 and miR-129-5p. The mRNA levels of MALAT1 were significantly enhanced in CCI rats. MALAT1 inhibition repressed the development of neuropathic pain and neuroinflammation. Additionally, miR-129-5p was decreased and HMGB1 was increased, both of which could be rectified by MALAT1 inhibition. Meanwhile, MALAT1 targeted miR-129-5p/HMGB1 axis. Finally, miR-129-5p suppression attenuated the inhibitory effect of MALAT1 inhibition on neuropathic pain and neuroinflammation development in CCI rats. The present study demonstrates that MALAT1 might modulate neuropathic pain via targeting miR-129-5p/HMGB1 axis. These findings may lead to a promising and efficacious clinical approach for the treatment of neuropathic pain.
Learn More >The locus coeruleus (LC) is one of the brainstem nuclei that may be activated during migraine attack. As LC contains neuromelanin, a by-product of norepinephrine synthesis, it can be delineated in vivo using neuromelanin sensitive magnetic resonance imaging (MRI). The neuromelanin content in LC has been suggested to reflect previous LC activation. We investigated LC MRI contrast in patients with migraine with aura (MWA) and its correlation with migraine features.
Learn More >This cross-sectional study examined the association between adverse childhood experiences (ACEs) and history of frequent headaches (including migraine) among children 3-17 years old using data from the 2016 and 2017 U.S. National Survey of Children's Health (NSCH).
Learn More >: Treatment for chronic pruritus ranges from use of topical formulations to newer biologic agents. Targeting treatment to the underlying etiology is key in reducing the burden of disease while avoiding systemic or adverse effects.: This review details the effective medical treatments used in various etiologies of chronic itch with a focus on the potential adverse effects and safety data available for each.: New drug developments in the areas of neural signaling and immune targeting show great promise for the future of chronic itch treatment. These new therapies broaden the available treatment options but also pose new considerations for safety and adverse effects.
Learn More >To investigate whether the self-treatment of migraine among neurologists and pain specialists corresponds to national medical guidelines and treatment of patients.
Learn More >Exposure to prenatal maternal stress impacts adult behavioral outcomes and has been suggested as a risk factor for chronic pain. However, the neurobiological mechanisms implicated are not well-characterized. In this study, we analyzed the effect of a prenatal maternal stress on the development of neuropathic pain-related behaviours and gene expression in the frontal cortex and hippocampus in adult offspring following chronic constriction injury of the sciatic nerve in male and female CD1 mice. Nerve injury-induced mechanical hypersensitivity was amplified in both male and female prenatally-stressed offspring, suggesting that prenatal stress exacerbates pain after injury. Analysis of mRNA expression of genes related to epigenetic regulation and stress responses in the frontal cortex and hippocampus, brain structures implicated in chronic pain, showed distinct sex and region-specific patterns of dysregulation. In general, mRNA expression was most frequently altered in the male hippocampus and effects of prenatal stress were more prevalent than effects of nerve injury in both supraspinal areas. These findings demonstrate the impact of prenatal stress on behavioral sensitivity to a painful injury. Changes in the expression of epigenetic- and stress-related genes suggest a possible mechanism by which the early life stress becomes embedded in the central nervous system. Increased understanding of the interactions among early-life stress, sex, and pain may lead to the identification of novel therapeutic targets and epigenetic drugs for the treatment of chronic pain disorders.
Learn More >Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.
Learn More >Pain is a classical sign of inflammation, and sensitization of primary sensory neurons (PSN) is the most important mediating mechanism. This mechanism involves direct action of inflammatory mediators such as prostaglandins and sympathetic amines. Pharmacologic control of inflammatory pain is based on two principal strategies: (i) non-steroidal anti-inflammatory drugs targeting inhibition of prostaglandin production by cyclooxygenases and preventing nociceptor sensitization in humans and animals; (ii) opioids and dipyrone that directly block nociceptor sensitization via activation of the NO signaling pathway. This review summarizes basic concepts of inflammatory pain that are necessary to understand the mechanisms of peripheral NO signaling that promote peripheral analgesia; we also discuss therapeutic perspectives based on the modulation of the NO pathway.
Learn More >Studies of the relation of fibromyalgia (FM) and widespread pain (WSP) to mortality have differed as to the presence or absence of an association and the extent of cause-specific mortality. However, no studies have investigated which definitions of FM and WSP associate with mortality, nor of FM mortality in other diseases. We investigated these issues and the meaning of mortality in patients with FM.
Learn More >AIMS The covalent linking of non-steroidal anti-inflammatory drugs (NSAIDs) to a hydrogen sulfide (H2S)-releasing moiety has been shown to dramatically reduce gastrointestinal (GI) damage and bleeding, as well as increasing anti-inflammatory and analgesic potency. We have tested the hypothesis that a H2S-releasing derivative of ketoprofen (ATB-352) would exhibit enhanced efficacy without significant GI damage in a mouse model of allodynia/hyperalgesia. RESULTS ATB-352 was significantly more potent as an analgesic than ketoprofen, and did not elicit GI damage. Pretreatment with a cannabinoid receptor-1 antagonist (AM251) significantly reduced the analgesic effects of ATB-352. The CB-1 antagonist exacerbated GI damage when co-administered with ketoprofen, but GI damage was not induced by the combination of ATB-352 and the CB-1 antagonist. ATB-352 was substantially more potent than ketoprofen as an inhibitor of fatty acid amide hydrolase, consistent with a contribution of endogenous cannabinoids to the analgesic effects of this drug. Blood anandamide levels were significantly depressed by ketoprofen, but remained unchanged after treatment with ATB-352. INNOVATION Ketoprofen is a potent analgesic, but its clinical use is significantly limited by its propensity to cause significant ulceration and bleeding in the GI tract. Covalently linking an H2S-releasing moiety to ketoprofen profoundly reduces the GI toxicity of the drug, while boosting the analgesic effectiveness.
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