Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

AbstractImpaired intestinal mucosal integrity during colitis involves the peroxisome proliferator-activated receptor- γ (PPARγ), an important anti-inflammatory factor in intestinal mucosa homoeostasis, which is a potential target in colitis. Recurrent chronic pain is a vital pathogenetic feature of colitis. Nevertheless, potential functions of PPARγ in the colitis-associated hyperalgesia remain unclear. This stu dy aimed to investigate biological roles of pioglitazone in relieving colitis-associated pain hypersensitivity by a PPARγ tight junction protein-dependent mechanism during the course of dextran sodium sulfate (DSS)-induced intestinal inflammation. The DSS-induced colitis model was generated in C57B L/6 mice. Changes in colitis induced the injury of intestinal mucosal barrier and hyperalgesia after a 6-day treatment of pioglitazone (25 mg/kg, IP injection) were assessed through immunofluorescent, hematoxylin and eosin (H&E) staining, western blot analysis, and determination of paw withdrawal mechanical threshold. A significant reduction of paw withdrawal mechanical threshold occurred after DSS treatment. Follow-up data showed that systematic administration of PPAR γ agonist pioglitazone ameliorated the DSS-induced colitis and the development of colitis-associated hyperalgesia by repairing the intestinal mucosal barrier. The tight junction proteins ZO-1 and Claudin-5 were upregulated by PPARγ signaling, which in turn promoted the...
Source: Inflammation - Category: Allergy & Immunology Source Type: research

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It has been proposed that complex regional pain syndrome (CRPS) is a post-traumatic autoimmune disease. Previously, we observed that B cells are required for the full expression of CRPS-like changes in a mouse tibia fracture model and that serum immunoglobulin M (IgM) antibodies from fracture mice have pronociceptive effects in muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of injecting CRPS patient serum or antibodies into muMT fracture mice by measuring hind paw allodynia and unweighting changes. Complex regional pain syndrome serum binding was measured against autoantigens pre...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood–spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXC...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionSimultaneous administration of muscimol and endomorphine ‐1 could be a new candidate for alleviation of pain resulting from spinal cord injury.
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusions: The complex clinical situation of each individual patient must be weighed against the risks and benefits of each medication, as reviewed in this paper, to determine the ideal treatment strategy for chronic spinal cord injury-related pain. PMID: 32182196 [PubMed - as supplied by publisher]
Source: Journal of Spinal Cord Medicine - Category: Orthopaedics Tags: J Spinal Cord Med Source Type: research
ConclusionsThe development of an injury unbalances the proteome of the local neural tissue, neurons, and glial cells, and shifts the proteomic profile to a pain producing state. This study demonstrates the reversal of the injury ‐induced proteomic state by applying conventional SCS therapy. Additional studies looking at variations in electrical parameters are needed to optimize SCS.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Basic Research Source Type: research
Opioid receptors comprise μ (MOP), δ (DOP), κ (KOP), and nociceptin/orphanin FQ (NOP) receptors. Opioids are agonists of MOP, DOP, and KOP receptors, whereas nociceptin/orphanin FQ (N/OFQ) is an agonist of NOP receptors. Activation of all four opioid receptors in neurons can induce analgesia in animal models, but the most clinically relevant are MOP receptor agonists (e.g., morphine, fentanyl). Opioids can also affect the function of immune cells, and their actions in relation to immunosuppression and infections have been widely discussed. Here, we analyze the expression and the role of opioid receptors in p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The future of healthcare is shaping up in front of our very eyes with advances in digital technologies, such as artificial intelligence, VR/AR, 3D-printing, robotics or nanotechnology. We have to familiarize with the latest developments in order to be able to control technology and not the other way around. The future of healthcare lies in working hand-in-hand with technology and healthcare workers have to embrace emerging technologies in order to stay relevant in the coming years. Be bold, curious and informed! Are you afraid that robots will take over the jobs of nurses, doctors and other healthcare professionals? Are y...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Future of Medicine 3d printing AI artificial intelligence augmented reality genetics Health Healthcare nanotechnology Personalized medicine pharma pharmacology robotics virtual reality wearables GC1 Source Type: blogs
Molecules, Vol. 25, Pages 1120: Building and Testing PPARγ Therapeutic ELB00824 with an Improved Therapeutic Window for Neuropathic Pain Molecules doi: 10.3390/molecules25051120 Authors: Westlund Zhang Effective, non-addictive therapeutics for chronic pain remain a critical need. While there are several potential therapeutics that stimulate anti-inflammatory mechanisms to restore homeostasis in the spinal dorsal horn microenvironment, the effectiveness of drugs for neuropathic pain are still inadequate. The convergence of increasing knowledge about the multi-factorial mechanisms underlying neuropathic pai...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
CONCLUSION: This is the first application of graphical modelling in studying spasticity in people living with spinal cord injury. The results can be used as a basis for studies aiming to optimize rehabilitation interventions in people with moderate-to-severe spasticity. PMID: 32103278 [PubMed - as supplied by publisher]
Source: Journal of Rehabilitation Medicine - Category: Rehabilitation Tags: J Rehabil Med Source Type: research
Abstract Neuropathic pain is a chronic pain characterized by injury to the central or peripheral nervous system and that most often causes disability in individuals. Among the mechanisms involved in central sensitization during neuropathic pain are cytokines and chemokines released by spinal glial cells; however, these mechanisms are not well elucidated. Thus, the present study aimed to investigate the involvement of Chemokine (C-X-C motif) ligand 1 (CXCL1) and glial cells in this process. Male Wistar rats weighing 220-240 g were used and underwent a neuropathic pain model induced by chronic constriction injury ...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
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