Suppression of neuropathic pain in the circadian clock–deficient <i>Per2m/m</i> mice involves up-regulation of endocannabinoid system

DOI PDF 参考文献65件 オープンアクセス
  • Wakaba Yamakawa
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Sai Yasukochi
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Yuya Tsurudome
    Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University , Yamaguchi, 756-0884 , Japan
  • Naoki Kusunose
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Yuta Yamaguchi
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Akito Tsuruta
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Naoya Matsunaga
    Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Kentaro Ushijima
    Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University , Yamaguchi, 756-0884 , Japan
  • Satoru Koyanagi
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Shigehiro Ohdo
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University , Fukuoka, 812-8582 , Japan
  • Eric Klann
    editor

説明

<jats:title>Abstract</jats:title> <jats:p>Neuropathic pain often results from injuries and diseases that affect the somatosensory system. Disruption of the circadian clock has been implicated in the exacerbation of the neuropathic pain state. However, in this study, we report that mice deficient in a core clock component Period2 (Per2m/m mice) fail to develop tactile pain hypersensitivity even following peripheral nerve injury. Similar to male wild-type mice, partial sciatic nerve ligation (PSL)-Per2m/m male mice showed activation of glial cells in the dorsal horn of the spinal cord and increased expression of pain-related genes. Interestingly, α1D-adrenergic receptor (α1D-AR) expression was up-regulated in the spinal cord of Per2m/m mice, leading to increased production of 2-arachidonoylglycerol (2-AG), an endocannabinoid receptor ligand. This increase in 2-AG suppressed the PSL-induced tactile pain hypersensitivity. Furthermore, intraspinal dorsal horn injection of adeno-associated viral vectors expressing α1D-AR also attenuated pain hypersensitivity in PSL-wild-type male mice by increasing 2-AG production. Our findings reveal an uncovered role of the circadian clock in neuropathic pain disorders and suggest a link between α1D-AR signaling and the endocannabinoid system.</jats:p>

収録刊行物

  • PNAS Nexus

    PNAS Nexus 3 (1), 2023-12-21

    Oxford University Press (OUP)

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