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Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex.
Pain. 2011 Jun; 152(6):1358-1372.PAIN

Abstract

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.

Authors+Show Affiliations

Department of Toxicology, Hoshi University, School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York City, NY 10065-6399, USA Cancer Pathophysiology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan Division of Palliative Medicine, Wakayama Medical University Hospital, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-8510, Japan Department of Psychiatry, Nihon University, School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8601, Japan Palliative Care Unit, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan Department of Palliative Medicine, Palliative Care Team, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21396773

Citation

Narita, Minoru, et al. "Sleep Disturbances in a Neuropathic Pain-like Condition in the Mouse Are Associated With Altered GABAergic Transmission in the Cingulate Cortex." Pain, vol. 152, no. 6, 2011, pp. 1358-1372.
Narita M, Niikura K, Nanjo-Niikura K, et al. Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex. Pain. 2011;152(6):1358-1372.
Narita, M., Niikura, K., Nanjo-Niikura, K., Narita, M., Furuya, M., Yamashita, A., Saeki, M., Matsushima, Y., Imai, S., Shimizu, T., Asato, M., Kuzumaki, N., Okutsu, D., Miyoshi, K., Suzuki, M., Tsukiyama, Y., Konno, M., Yomiya, K., Matoba, M., & Suzuki, T. (2011). Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex. Pain, 152(6), 1358-1372. https://doi.org/10.1016/j.pain.2011.02.016
Narita M, et al. Sleep Disturbances in a Neuropathic Pain-like Condition in the Mouse Are Associated With Altered GABAergic Transmission in the Cingulate Cortex. Pain. 2011;152(6):1358-1372. PubMed PMID: 21396773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex. AU - Narita,Minoru, AU - Niikura,Keiichi, AU - Nanjo-Niikura,Kana, AU - Narita,Michiko, AU - Furuya,Masaharu, AU - Yamashita,Akira, AU - Saeki,Mai, AU - Matsushima,Yuki, AU - Imai,Satoshi, AU - Shimizu,Toshikazu, AU - Asato,Megumi, AU - Kuzumaki,Naoko, AU - Okutsu,Daiki, AU - Miyoshi,Kan, AU - Suzuki,Masami, AU - Tsukiyama,Yoshi, AU - Konno,Michiko, AU - Yomiya,Kinomi, AU - Matoba,Motohiro, AU - Suzuki,Tsutomu, Y1 - 2011/03/10/ PY - 2010/06/08/received PY - 2011/02/04/revised PY - 2011/02/07/accepted PY - 2011/3/15/entrez PY - 2011/3/15/pubmed PY - 2011/9/29/medline SP - 1358 EP - 1372 JF - Pain JO - Pain VL - 152 IS - 6 N2 - 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. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21396773/Sleep_disturbances_in_a_neuropathic_pain_like_condition_in_the_mouse_are_associated_with_altered_GABAergic_transmission_in_the_cingulate_cortex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-201106000-00024 DB - PRIME DP - Unbound Medicine ER -