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Previous studies have demonstrated that weight loss has been shown to improve pain in weight-bearing joints, and more recent studies suggest that weight loss may be accompanied by improvements in pain in non-weight-bearing regions. In previous work, we demonstrated that these symptoms improve substantially in patients with obesity undergoing 12 weeks of a very low-energy diet (VLED) restricted to 800 kcal as part of a weight-loss program. Preclinical models also have shown analgesic effects of calorie restriction. The purpose of the current observational study was to determine the time course and trajectory of improvement in pain and other symptoms, especially during the early phase of a VLED intervention, prior to major weight loss.
Learn More >The sensations of touch and pain are fundamental components of our daily life, which can transport vital information about the surroundings and provide protection to our bodies. In this study, the transmission process of sensing pressure stimuli to dorsal root neurons (nociceptors) was simulated using electronic devices. In this regard, we proposed and experimentally demonstrated a biomimetic nociceptor system with tactile perception. In this system, the sensing paper as E-skin simulates the biological skin to sense external pressure stimulation and generate electrical signals, while the threshold switching memristor simulates the biological nociceptor to receive and process the receptor signals. The W/VO/Pt memristor exhibits all key features of nociceptors including threshold, relaxation, "no adaptation" and sensitization phenomena of allodynia and hyperalgesia. The E-skin shows high sensitivity and a broad sensing range and is capable of monitoring different human movements and physiological signals. With the bio-inspired artificial tactile nociceptive system, the threshold and sensitization properties under pressure stimuli are obtained successfully. Notably, this system could be used as an artificial tactile alarm system to demonstrate the potential applicability of humanoid robots. Thus, the present work is of great significance to the development of hardware architecture in artificial intelligence systems and replacement neuroprosthetics.
Learn More >Mast cells are widely distributed in various parts of the human body and play a vital role in the progression of many diseases. Recently, the close relationship between mast cells and acupoints was elucidated, and the role of mast cells in acupuncture analgesia has attracted the attention of researchers worldwide. Using mast cells, acupuncture analgesia and acupoint as key words to search CNKI, PubMed, Web of Science and other databases, combining the representative articles in these databases with the published research papers of our group, we summarized: The enrichment of mast cells and the dense arrangement of collagen fibers, microvessels, and nerves form the basis for acupoints as the reaction sites of acupuncture; acupuncture can cause the deformation of collagen fibers and activate TRPV channels on mast cells membrane, so as to stimulate mast cells to release bioactive substances and activate nerve receptors to generate analgesic effect; system biology models are set up to explain the quantitative process of information initiation and transmission at acupuncture points, and indicate that the acupuncture effect depends on the local mast cells density. In a conclusion, this review will give a scientific explanation of acupuncture analgesia from the material basis of acupoints, the local initiation, and afferent biological mechanism.
Learn More >Oxaliplatin-induced peripheral neuropathy (OIPN) is an unwanted side effect of oxaliplatin chemotherapy treatment. OIPN manifests in an acute phase that lasts a few days after injection and a persistent phase that may become chronic. Currently, there is no consensus about a clinically applicable, quantitative, and objective measure of OIPN.
Learn More >Fentanyl derivatives (FENS) belongs to the class of Novel Synthetic Opioids that emerged in the illegal drug market of New Psychoactive Substances (NPS). These substances have been implicated in many cases of intoxication and death with overdose worldwide. Therefore, the aim of this study is to investigate the pharmaco-dynamic profiles of three fentanyl (FENT) analogues: Acrylfentanyl (ACRYLF), Ocfentanyl (OCF) and Furanylfentanyl (FUF). In vitro, we measured FENS opioid receptor efficacy, potency, and selectivity in calcium mobilization studies performed in cells coexpressing opioid receptors and chimeric G proteins and their capability to promote the interaction of the mu receptor with G protein and β-arrestin 2 in bioluminescence resonance energy transfer (BRET) studies. In vivo, we investigated the acute effects of the systemic administration of ACRYLF, OCF and FUF (0.01-15 mg/kg i.p.) on mechanical and thermal analgesia, motor impairment, grip strength and cardiorespiratory changes in CD-1 male mice. Opioid receptor specificity was investigated in vivo using naloxone (NLX; 6 mg/kg i.p) pre-treatment. In vitro, the three FENS were able to activate the mu opioid receptor in a concentration dependent manner with following rank order potency: FUF > FENT=OCF > ACRYLF. All compounds were able to elicit maximal effects similar to that of dermorphin, with the exception of FUF which displayed lower maximal effects thus behaving as a partial agonist. In the BRET G-protein assay, all compounds behaved as partial agonists for the β-arrestin 2 pathway in comparison with dermorphin, whereas FUF did not promote β-arrestin 2 recruitment, behaving as an antagonist. In vivo, all the compounds increased mechanical and thermal analgesia with following rank order potency ACRYLF = FENT > FUF > OCF and impaired motor and cardiorespiratory parameters. Among the substances tested, FUF showed lower potency for cardiorespiratory and motor effects. These findings reveal the risks associated with the use of FENS and the importance of studying the pharmaco-dynamic properties of these drugs to better understand possible therapeutic interventions in the case of toxicity.
Learn More >The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans.
Learn More >The CDC cautioned against prescribing opioids for long-term chronic pain because opioid use disorder (OUD) risk was greater compared to short-term use for acute pain. The study objective was to describe rates and characteristics of respondents prescribed opioids for long-term chronic and short-term acute pain. National Health Interview Survey respondents for 2019 aged 18 years and over were examined (n = 31,997). Bivariate and multivariable models demonstrated opioid use for long-term and acute pain relative to sociodemographic characteristics. About 12.3% of US adults took opioids in the last 12 months, and among those with chronic pain who had been prescribed opioids in the last 3 months, over half took opioids every day. The odds of taking opioids for long-term chronic pain decreased with increasing income and increased with advancing age. Opioid prescribing diverged from CDC recommendations. Less affluent older adults may be at increased risk for OUD.
Learn More >Suicidality is a common public health concern in young people. Previous research has highlighted pain as a key correlate of suicidality in young people. However, the long-term experience of pain may vary between individuals, and the relationship between distinct pain trajectories and suicidality is poorly understood. This study aims to describe the number and nature of distinct pain trajectories, their demographic and clinical correlates, including baseline suicidality, and whether identified pain trajectories may predict future suicidality. Secondary data analyses were performed, using longitudinal data from the British Child and Adolescent Mental Health Survey (N = 7977), collected at five timepoints between 2004 and 2007 on a population-based sample of UK youth (5-16 years). Data were collected from up to three respondents (parents, teachers, and 11 + year-olds). Latent Class Growth Analysis was used to identify distinct pain trajectories, explore predictors of these trajectories, and establish whether trajectories predicted future suicidality. We identified the following four pain trajectories: increasing (33.6%), decreasing (4.5%), persistent/recurrent probability of pain (15.7%), and no pain (46.2%). Pain trajectories were associated with unique demographic and clinical correlates. Only the persistent/recurrent (vs. no-pain) trajectory was predicted by baseline suicidality (aOR = 2.24; 95% bootstrap-CI = 1.59-3.26). Furthermore, the persistent/recurrent trajectory predicted future suicidality (aOR = 1.03, 95% bootstrap-CI = 1.01-1.06), after controlling for baseline suicidality, psychiatric disorder, age, and gender. Findings provide a better understanding of correlates associated with distinct pain trajectories and long-term risk of suicidality in young people, suggesting a bidirectional pain-suicidality association and emphasising the need of targeted support for young people with persistent/recurrent pain.
Learn More >Neuropathic pain is one of the primary forms of chronic pain and is the consequence of the somatosensory system's direct injury or disease. It is a relevant public health problem that affects about 10% of the world's general population. In neuropathic pain, alteration in neurotransmission occurs at various levels, including the dorsal root ganglia, the spinal cord, and the brain, resulting from the malfunction of diverse molecules such as receptors, ion channels, and elements of specific intracellular signaling pathways. In this context, there have been exciting advances in elucidating neuropathic pain's cellular and molecular mechanisms in the last decade, including the possible role that long non-coding RNAs (lncRNAs) may play, which open up new alternatives for the development of diagnostic and therapeutic strategies for this condition. This review focuses on recent studies associated with the possible relevance of lncRNAs in the development and maintenance of neuropathic pain through their actions on the functional expression of ion channels. Recognizing the changes in the function and spatio-temporal patterns of expression of these membrane proteins is crucial to understanding the control of neuronal excitability in chronic pain syndromes.
Learn More >Metabolite levels in peripheral body fluids can correlate with attack features in migraine patients, which underscores the potential of plasma metabolites as possible disease biomarkers. Migraine headache can be preceded by an aura that is caused by cortical spreading depolarization (CSD), a transient wave of neuroglial depolarization. We previously identified plasma amino acid changes after CSD in familial hemiplegic migraine type 1 (FHM1) mutant mice that exhibit increased neuronal excitability and various migraine-related features. Here, we aimed to uncover lipid metabolic pathways affected by CSD, guided by findings on the involvement of lipids in hemiplegic migraine pathophysiology. Using targeted lipidomic analysis, we studied plasma lipid metabolite levels at different time points after CSD in wild-type and FHM1 mutant mice. Following CSD, the most prominent plasma lipid change concerned a transient increase in PGD, which lasted longer in mutant mice. In wild-type mice only, levels of anti-inflammatory lipid mediators DPAn-3, EPA, ALA, and DHA were elevated 24 h following CSD compared to Sham-treated animals. Given the role of PGs and neuroinflammation in migraine pathophysiology, our findings underscore the potential of monitoring peripheral changes in lipids to gain insight in central brain mechanisms.
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