Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex
Autor: | Kinomi Yomiya, Daiki Okutsu, Megumi Asato, Satoshi Imai, Akira Yamashita, Tsutomu Suzuki, Keiichi Niikura, Naoko Kuzumaki, Yuki Matsushima, Masami Suzuki, Michiko Narita, Yoshi Tsukiyama, Minoru Narita, Motohiro Matoba, Masaharu Furuya, Michiko Konno, Toshikazu Shimizu, Kan Miyoshi, Kana Nanjo-Niikura, Mai Saeki |
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Rok vydání: | 2011 |
Předmět: |
Pain Threshold
Sleep Wake Disorders Cingulate cortex GABA Plasma Membrane Transport Proteins Pyridines Microdialysis Midazolam Nipecotic Acids Anisoles Gyrus Cinguli Mice Physical Stimulation Cortex (anatomy) Glial Fibrillary Acidic Protein Reflex medicine Animals Hypnotics and Sedatives GABA transporter RNA Messenger gamma-Aminobutyric Acid Pain Measurement Analysis of Variance Mice Inbred ICR biology Electromyography business.industry Chronic pain Electroencephalography Nerve injury medicine.disease Mice Inbred C57BL Zolpidem Disease Models Animal Anesthesiology and Pain Medicine medicine.anatomical_structure Gene Expression Regulation nervous system Neurology Hyperalgesia Neuropathic pain biology.protein GABAergic Neurology (clinical) Sciatic nerve Sciatic Neuropathy medicine.symptom business Neuroscience |
Zdroj: | Pain. 152:1358-1372 |
ISSN: | 0304-3959 |
DOI: | 10.1016/j.pain.2011.02.016 |
Popis: | Insomnia is a common problem for people with chronic pain. Cortical GABAergic neurons are part of the neurobiological substrate that underlies homeostatic sleep regulation. In the present study, we confirmed that sciatic nerve ligation caused thermal hyperalgesia and tactile allodynia in mice. In this experimental model for neuropathic pain, we found an increase in wakefulness and a decrease in non-rapid eye movement sleep under a neuropathic pain-like state. Under these conditions, membrane-bound GABA (γ-aminobutyric acid) transporters (GATs) on activated glial fibrillary acidic protein-positive astrocytes were significantly increased in the cingulate cortex, and extracellular GABA levels in this area after depolarization were rapidly decreased by nerve injury. Furthermore, sleep disturbance induced by sciatic nerve ligation was improved by the intracingulate cortex injection of a GAT-3 inhibitor. These findings provide novel evidence that sciatic nerve ligation decreases extracellular-released GABA in the cingulate cortex of mice. These phenomena may, at least in part, explain the insomnia in patients with neuropathic pain. Neuropathic pain-like stimuli suppress the GABAergic transmission with increased GABA (γ-aminobutyric acid) transporters located on activated astrocytes in the cingulate cortex related to sleep disturbance. |
Databáze: | OpenAIRE |
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