TRPV1 promotes opioid analgesia during inflammation

Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute inflammation in humans or mice enhances the analgesic properties of opioids, there is much interest in determining the inflammatory transducers that prime opioid receptor signaling in primary afferent nociceptors. Here, we found that activation of the transient receptor potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) signaling pathway that was accompanied by the shuttling of the scaffold protein β-arrestin2 to the nucleus. The nuclear translocation of β-arrestin2 in turn prevented its recruitment to the μ-opioid receptor (MOR), the subsequent internalization of agonist-bound MOR, and the suppression of MOR activity that occurs upon receptor desensitization. Using the complete Freund’s adjuvant (CFA) inflammatory pain model to examine the role of TRPV1 in regulating endogenous opioid analgesia in mice, we found that naloxone methiodide (Nal-M), a peripherally restricted, nonselective, and competitive opioid receptor antagonist, slowed the recovery from CFA-induced hypersensitivity in wild-type, but not TRPV1-deficient, mice. Furthermore, we showed that inflammation prolonged morphine-induced antinociception in a mouse model of opioid receptor desensitization, a process that depended on TRPV1. Together, our data reveal a TRPV1-mediated signaling pathway that serves as an endogenous pain-resolution me...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

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Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons. Brain Behav Immun. 2020 Mar 20;: Authors: He L, Han G, Wu S, Du S, Zhang Y, Liu W, Jiang B, Zhang L, Xia S, Jia S, Hannaford S, Xu Y, Tao YX Abstract Toll like receptor 7 (TLR7) is expressed in neurons of the dorsal root ganglion (DRG), but whether it contributes to neuropathic pain is elusive. We found that peripheral nerve injury caused by ligation of the fourth lumbar (L4) spinal nerve (SNL) or chronic constriction injury of sciatic nerve led to a significant increase in the expression of TLR7...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
Abstract CONTEXT: Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear. OBJECTIVE: To investigate the molecular effects of yokukansan on neuroinflammation in U373 MG glioblastoma astrocytoma cells, which express a functional high-affinity neurokinin 1 receptor (substance P receptor), and produce interleukin (IL)-6 and IL-8 in response to stimulation by substance P (SP). MATERIALS AND METHODS: We assessed the effect of yokukansan on expression of ERK1/2, P38 MAP...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - Category: Endocrinology Authors: Tags: Endocr Metab Immune Disord Drug Targets Source Type: research
Publication date: 15 December 2019Source: Life Sciences, Volume 239Author(s): Wanli Ji, Kun Liang, Rui An, Xinhong WangAbstractAimsCurrently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastritis.M...
Source: Life Sciences - Category: Biology Source Type: research
Publication date: Available online 14 November 2019Source: Life SciencesAuthor(s): Wanli Ji, Kun Liang, Rui An, Xinhong WangAbstractAimsCurrently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastri...
Source: Life Sciences - Category: Biology Source Type: research
This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression https://www.fightaging.org/archives/2019/07/gene-therapy-in-mice-alters-the-balance-of-macrophage-phenotypes-to-slow-atherosclerosis-progression/ Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
G, Sanogo I Abstract INTRODUCTION: The diagnosis of chronic myeloid leukemia is based on the presence of translocation t(9,22). Additional cytogenetic abnormalities may exist at diagnosis and have prognostic value. The authors evaluated the relationship between these additional chromosomal abnormalities, clinical presentation, and therapeutic response. METHOD: In a retrospective and comparative study from 2005 to 2015, at Yopougon university hospital, 51 cases of myeloid leukemia were selected, including 22 cases with additional chromosomal abnormalities. RESULTS: Thirteen types of additional Ph1 abnorma...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Vinay Kumar1, Workineh Torben2, Joshua Mansfield3, Xavier Alvarez3, Curtis Vande Stouwe4, Jian Li5, Siddappa N. Byrareddy6, Peter J. Didier3, Bapi Pahar3, Patricia E. Molina4,7 and Mahesh Mohan3* 1Nektar Therapeutics, South San Francisco, CA, United States 2Department of Biological Sciences, LSU, Alexandria, LA, United States 3Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States 4Department of Physiology, LSUHSC, New Orleans, LA, United States 5Department of Global Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
A Symphytum officinale Root Extract Exerts Anti-inflammatory Properties by Affecting Two Distinct Steps of NF-κB Signaling Jacqueline Seigner1, Marc Junker-Samek2, Alberto Plaza2, Gilda D‘Urso3, Milena Masullo3, Sonia Piacente3, Yvonne M. Holper-Schichl4*† and Rainer de Martin1*† 1Department of Vascular Biology, Medical University of Vienna, Vienna, Austria 2R&D, Procter &Gamble Health, Darmstadt, Germany 3Dipartimento di Farmacia, Università degli Studi di Salerno, Salerno, Italy 4Drehm Pharma GmbH, Vienna, Austria Symphytum officinale, commonly known as comfrey, constitute...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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