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Folic acid attenuates chronic visceral pain by reducing Clostridiales abundance and hydrogen sulfide production.

Irritable bowel syndrome (IBS) related chronic visceral pain affects 20% of people worldwide. The treatment options are very limited. Although the scholarly reviews have appraised the potential effects of the intestinal microbiota on intestinal motility and sensation, the exact mechanism of intestinal microbiota in IBS-like chronic visceral pain remains largely unclear. The purpose of this study is to investigate whether Folic Acid (FA) attenuated visceral pain and its possible mechanisms.

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Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

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The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.

Long-term use of opioids such as morphine has negative side effects, such as morphine analgesic tolerance and morphine-induced hyperalgesia (MIH). These side effects limit the clinical use and analgesic efficacy of morphine. Elucidation of the mechanisms and identification of feasible and effective methods or treatment targets to solve this clinical phenomenon are important. Here, we discovered that YTHDF1 and TNF receptor-associated factor 6 (TRAF6) are crucial for morphine analgesic tolerance and MIH. The m6A reader YTHDF1 positively regulated the translation of TRAF6 mRNA, and chronic morphine treatments enhanced the m6A modification of TRAF6 mRNA. TRAF6 protein expression was drastically reduced by YTHDF1 knockdown, although TRAF6 mRNA levels were unaffected. By reducing inflammatory markers such as IL-1β, IL-6, TNF-α and NF-κB, targeted reduction of YTHDF1 or suppression of TRAF6 activity in ventrolateral periaqueductal gray (vlPAG) slows the development of morphine analgesic tolerance and MIH. Our findings provide new insights into the mechanism of morphine analgesic tolerance and MIH indicating that YTHDF1 regulates inflammatory factors such as IL-1β, IL-6, TNF-α and NF-κB by enhancing TRAF6 protein expression.

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The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

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Understanding how college students characterise and cope with chronic pain: a thematic analysis of expressive writing samples.

College students who experience chronic pain are a frequently overlooked population. This research attempts to provide insight into the language that college students use to describe their experiences with chronic pain, challenges they face and coping strategies they use. Over the course of 4 consecutive days, participants responded to an expressive writing prompt asking them to reflect on their emotions and thoughts related to being a college student with chronic pain. Writing samples were then analysed to identify themes pertaining to words with a positive or negative emotional valence, terms used to characterise pain, metaphors used to describe pain, challenges faced, and positive and negative coping strategies used. Results showed that participants were more likely to use negatively valenced words than positively valenced words to describe their pain. Several common words and phrases were used to characterise pain, including metaphors. Finally, participants reported a number of challenges associated with their lived-experience of chronic pain, as well as positive and negative strategies used to cope with those challenges. These findings help to put into perspective the language used to understand, and attempt to cope with, the challenges faced by college students experiencing chronic pain. Research must continue to investigate the needs of this population so that they can be properly supported physically, emotionally, socially and academically.

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Symptom descriptors and patterns in lumbar radicular pain caused by disc herniation: a 1-year longitudinal cohort study.

The objective of the present study was to explore the diversity, quality, severity and distribution of symptoms in patients with radicular pain and a lumbar disc herniation.

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TRPV1 and TRPM8 antagonists reduce cystitis-induced bladder hypersensitivity via inhibition of different sensitised classes of bladder afferents in guinea pigs.

Interstitial cystitis (=painful bladder syndrome) is a chronic bladder syndrome characterised by pelvic and bladder pain, urinary frequency and urgency, and nocturia. Transient receptor potential (TRP) channels are an attractive target in reducing the pain associated with interstitial cystitis. The current study aims to determine the efficacy of combination of TRP vanilloid 1 (TRPV1) and TRP melastatin 8 (TRPM8) channel inhibition in reducing the pain associated with experimental cystitis in guinea pigs.

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RAR-alpha: Creator, protector, and tormentor.

Retinoic acid receptors are important for homeostatic synaptic plasticity and have many beneficial effects within the brain. New work by Cao et al. uncovers a role for these receptors in driving neuropathic pain development, thus identifying a potential preventative therapeutic target.

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RAD-140 Drug-Induced Liver Injury.

RAD-140, one of the novel selective androgen receptor modulators (SARMs), has potent anabolic effects on bones and muscles with little androgenic effect. Despite the lack of approval for its clinical use, RAD-140 is readily accessible on the consumer market. Hepatotoxicity associated with the use of SARMs has only rarely been reported in the literature. A 24-year-old male presented with a 2-week history of diffuse abdominal pain, scleral icterus, pruritus, and jaundice. Prior to presentation, he had been taking the health supplement RAD-140 for muscle growth for 5 weeks. He had a cholestatic pattern of liver injury, with a peak total bilirubin of 38.5 mg/dL. Liver biopsy was supportive of a diagnosis of RAD-140-associated liver injury characterized pathologically by intracytoplasmic and canalicular cholestasis with minimal portal inflammation. Symptoms and liver injury resolved after cessation of the offending agent. To date, only select descriptions of the potential hepatoxicity associated with the use of SARMs, including RAD-140, have been published. Given their potential hepatoxicity and ready availability on the consumer market, RAD-140 and other SARMs should be used judiciously and under close clinical supervision until further hepatic safety data become available.

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Comparison of Neurological Manifestations in the Two Waves of COVID-19 Infection: A Cross-Sectional Study.

Coronavirus Disease-19 (COVID-19) is an ongoing pandemic caused by highly contagious virus severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) that has infected millions of people across the world. Most of the countries have seen two wave patterns of the pandemic. The second wave is potentially more challenging due to high influx of cases, differing properties of the emerging mutants, and other dynamics of the evolving pandemic. Neurological manifestations are common among COVID-19 positive patients. In this context, the present study attempts to compare the neurological manifestation in the first and second waves of COVID-19.

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