Effects of D-serine on tolerance to the antinociceptive effects of morphine

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Tokai University
• Principal Investigator: ITO Kenji 東海大学, 医学部, 准教授 (10317779)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: モルヒネ / 鎮痛耐性形成 / Dセリン / NMDA受容体 / dynorphin

Outline of Final Research Achievements

Chronic morohine administration induced mRNA expression of serine racemase in all brain regions and spinal cord and that of D-amino acid oxidase in forebrain of rats. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N- and C-terminals, respectively. Pretreatment with peptidase inhibitors augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50- or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with peptidase inhibitors induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or Dyn A (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat. These results indicated that administration of chronic morphine increased dynorphin A (1-17), and then induced nociception through NMDA receptors.

Free Research Field

麻酔科学