Antipruritus effect and antinociceptive effect of kappa opioid at the spinal level

• Project/Area Number: 26460697
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Shimane University
• Principal Investigator: Imamachi Noritaka 島根大学, 医学部, 准教授 (40325048)
• Co-Investigator(Kenkyū-buntansha): 齊藤 洋司 島根大学, 医学部, 教授 (50162243)
• Research Collaborator: Sakakihara Manabu 松江赤十字病院, 麻酔科 ; hattori Mai 島根大学, 医学部麻酔科学講座, 技術職員
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: κオピオイド受容体 / 鎮痒 / 鎮痛 / 痒み / オピオイド / κオピオイド受容体作動薬 / 術後痛 / 脊髄くも膜下腔 / モルヒネ / kappaオピオイド受容体作動薬 / 副作用

Outline of Final Research Achievements

The μ-opioid receptor (MOR) agonistinduced-itch is a serious adverse effect.We demonstrated that intrathecal κ-opioid receptor agonists（KOR） exert antipruritic effects on morphine-induced itch without affecting sedation in mice.The combination of intratheca morphine and intratheca KOR agonists produces more potent antinociceptive effects against a thermal stimulus compared with morphine alone.
We evaluated the effect of intraoperative pentazocine on the incidence of opioid-induced pruritus within the first 24 hours after administration of neuraxial opioids after cesarean delivery.Pentazocine reduced the overall incidence of pruritus within the first 24 hours.Pentazocine also reduced the
severity of pruritus.Pentazocine after delivery can reduce both the incidence and severity of pruritus in women who have received it opioids during cesarean delivery.

Research Products

• [Journal Article] Chronic Postsurgical Pain After Inguinal Hernia Surgery: Association with the Acute Postsurgical Pain: A Preliminary Study Based on Questionnaires. (2018)
  • Author(s): Imamachi N, Doi K, Watanab Y , Saito Y.
  • Journal Title: Shimane Journal of Medicine Science Volume: 34 (3) Pages: 93-97
  • Peer Reviewed
• [Journal Article] Prophylactic Pentazocine Reduces the Incidence of Pruritus After Cesarean Delivery Under Spinal Anesthesia With Opioids: A Prospective Randomized Clinical Trial. (2017)
  • Author(s): Hirabayashi M, Doi K, Imamachi N, Kishimoto T, Saito Y.
  • Journal Title: Anesth Analg. Volume: 124(6) Issue: 6 Pages: 1930-1934
  • DOI: 10.1213/ane.0000000000002060
  • NAID: 40021733047
  • Peer Reviewed
• [Journal Article] Reply to Dr Ruan (2016)
  • Author(s): Imamachi N, Saito Y
  • Journal Title: Reg Anesth Pain Med Volume: 41 Issue: 3 Pages: 414-5
  • DOI: 10.1097/aap.0000000000000383
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of Intrathecal κ-Opioid Receptor Agonist on Morphine-Induced Itch and Antinociception in Mice. (2016)
  • Author(s): Sakakihara M, Imamachi N, Saito Y.
  • Journal Title: Reg Anesth Pain Med. Volume: 41 Issue: 1 Pages: 69-74
  • DOI: 10.1097/aap.0000000000000326
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] (教育講演) 痒みの神経機構 (2016)
  • Author(s): 今町憲貴
  • Organizer: 日本臨床麻酔学会第36回大会
  • Place of Presentation: 高知市 ホテル日航高知旭ロイヤル
  • Year and Date: 2016-11-03
• [Presentation] Effects of intrathecal kappa opioid receptor agonist on intrathecal morphine-induced analgesia in a mouse model of the plantar incisional pain. (2015)
  • Author(s): Sakakihara M, Imamachi N, Saito Y
  • Organizer: American Society of Anesthesiologists 2015
  • Place of Presentation: San Diego （Ｕ.S.A)
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] マウス足底術後痛モデルにおけるモルヒネに対する脊髄くも膜下腔κオピオイド受容体作動薬の鎮痛効果の検討 (2015)
  • Author(s): 榊原 学, 今町 憲貴, 角田 尚紀, 服部 舞, 勝部 由貴子, 齊藤 洋司
  • Organizer: 日本麻酔科学会第62回学術集会
  • Place of Presentation: 神戸市（神戸ポートピアホテル・神戸国際展示場）
  • Year and Date: 2015-05-28
• [Presentation] 脊髄レベルでのモルヒネによる鎮痛・鎮静効果に対するκオピオイド受容体作動薬の効果 (2014)
  • Author(s): 榊原 学, 今町 憲貴, 齊藤 洋司
  • Organizer: 日本区域麻酔学会第1回学術集会
  • Place of Presentation: 岡山県岡山市岡山コンベンションセンター
  • Year and Date: 2014-04-25 – 2014-04-26
• [Book] 島大病院 ちょっと気になる健康講座２ 健康のはなし 8 術後鎮痛 (2016)
  • Author(s): 今町憲貴
  • Total Pages: 3
  • Publisher: 今井出版
• [Book] 新 麻酔科研修の素朴な疑問に答えます Ⅶ 局所麻酔薬・区域麻酔 077．局所麻酔薬の極量はどのようにして決められるか？ (2016)
  • Author(s): 今町憲貴, 齊藤洋司
  • Total Pages: 3
  • Publisher: メディカルサイエンス・インターナショナル