• Minoru Narita, Keiichi Niikura, Kana Nanjo-Niikura, Masaharu Furuya, Akira Yamashita, Mai Saeki, Yuki Matsushima, Satoshi Imai, Toshikazu Shimizu, Megumi Asato, Naoko Kuzumaki, Daiki Okutsu, Kan Miyoshi, Masami Suzuki, Yoshi Tsukiyama, Michiko Konno, Kinomi Yomiya, Motohiro Matoba, and Tsutomu Suzuki.
• Department of Toxicology, Hoshi University, School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. narita@hoshi.ac.jp
• Pain. 2011 Jun 1;152(6):1358-72.

AbstractInsomnia 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.Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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