Browse by Audience
Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischemia-reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into 5 groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data has shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioral parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress. This article is protected by copyright. All rights reserved.
Learn More >The spinal cord dorsal horn is the first relay station of the neural network for processing somatosensory information. High-throughput recording methods facilitate the study of sensory coding in the cortex but have not been successfully applied to study spinal cord circuitry until recently. Here, we review the development of the in vivo two-photon spinal calcium imaging preparation and biological findings from the first systematic characterization of the spinal response to cutaneous thermal stimuli, focusing on the difference between the coding of heat and cold, and the contribution of different peripheral inputs to thermosensory response in the spinal cord. Here we also report that knockout of TRPV1 channel impairs sensation of warmth, and somatostatin- and calbindin2-expressing neurons in the spinal dorsal horn preferentially respond to heat. Future work combining this technology with genetic tools and animal models of chronic pain will further elucidate the role of each neuronal type in the spinal thermosensory coding and their plasticity under pathological condition.
Learn More >Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino-acid insert within the TM3-TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission.
Learn More >Migraine is a common and severely disabling neurological disorder affecting millions of patients in Europe. Despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains poor, which is often attributed to a low availability of headache specialists. The aim of this study was to investigate the adherence to national guidelines and to assess the possible potential of optimized therapy regimens in migraine patients.
Learn More >Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition.
Learn More >The US National Pain Strategy focused attention on high-impact chronic pain and its restrictions. Although many interventions have been studied for chronic low-back pain, results are typically reported for heterogeneous samples. To better understand chronic pain and target interventions to those who most need care, more granular classifications recognizing chronic pain's impact are needed.
Learn More >Cannabinoids are proposed in a wide array of medical indications. Yet, the evaluation of adverse effects in controlled clinical studies, following the evidence-based model, has partly been by-passed. On the other hand, studies on the consequences of recreational use of cannabis and experimental studies bring some insights on the potential long-term consequences of cannabinoids use.
Learn More >To determine the association of medical marijuana legalization with prescription opioid utilization.
Learn More >Offset analgesia (OA) is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. Here we tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. Forty-eight participants continuously rated their pain experience during trials containing trains of heat stimuli delivered by peltier thermode. Stimuli were adjusted through either step-wise sequential increases of 2 C and decreases of 1 C or direct step increases of 1 C, up to a maximum of 46 C. Step durations (1, 2, 3, or 6 s) varied by trial. Pain ratings generally followed presented temperature, regardless of step condition or duration. For 6 s steps, offset analgesia was observed after each decrease, but the overall pain trajectory was unchanged. We found no evidence that sequential offsets could allow for little pain perception during noxious temperature presentation.
Learn More >Increasing pain during physical activity is as an important, but often poorly assessed, barrier to engaging in activity-based rehabilitation among people with chronic musculoskeletal pain. Preliminary work has addressed this problem by developing new clinical measures of sensitivity to physical activity (SPA). Indices of SPA are generated by evaluating how pain changes in relation to brief physical tasks. Three strategies have been identified for structuring SPA-related physical tasks (self-paced, standardized, and tailored). This cross-sectional study aimed to comparatively estimate the extent of the three SPA tasks' evoked pain responses, predictive value of pain severity and pain interference, and their underlying psychological and sensory constructs, among 116 adults with chronic musculoskeletal pain.
Learn More >