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Filename: controllers/Detail.php
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Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes.
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http://dx.doi.org/10.1073/pnas.1510137112 | DOI Listing |
Vopr Kurortol Fizioter Lech Fiz Kult
December 2024
Saratov State Medical University named after V. I. Razumovsky, Saratov, Russia.
Unlabelled: The problem of rational activation of functions of the central nervous system of a human remains highly relevant.
Objective: To analyze scientific data on the use of transcranial exposure method in obesity.
Results: The literature review presents current data on the effectiveness of non-invasive hardware brain neurostimulation in obese patients.
ACS Appl Bio Mater
December 2024
Polymers & Functional Materials Division, CSIR- Indian Institute of Chemical Technology, Hyderabad 500007, India.
Neurological disorders impact global health by affecting both central and peripheral nervous systems. Understanding the neurogenic processes, i.e.
View Article and Find Full Text PDFFront Cell Neurosci
December 2024
Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Psychiatry
December 2024
West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
Background: Psychiatric illness is thought to be a brain somatic crosstalk disorder. However, the existing phenomenology-based Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic framework overlooks various dimensions other than symptoms. In this study, we investigated the associations between peripheral blood test indexes with various symptom levels of major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) to explore the availability of peripheral blood test indexes.
View Article and Find Full Text PDFBrain
December 2024
School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
Convergent data, across species, paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function where it mediates the majority of neuronal inhibition.
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