Mechanism of opioid induced hyperalgesia and its prophylaxis in general anesthesia; an electrophysiological analysis

Research Project

Project/Area Number	15K20056
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Osaka City University
Principal Investigator	FUNAI Yusuke 大阪市立大学, 大学院医学研究科, 講師 (60722486)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords	痛覚過敏 / 全身麻酔薬 / 脊髄後角 / 鎮痛作用 / 麻酔薬 / パッチクランプ法 / パッチクランプ
Outline of Final Research Achievements	We found out that general anesthetics strongly affected on synaptic transmission in the spinal cord dorsal horn in early experiment, therefore more detailed examinations were required. Sevoflurane(SEV)(0.1-2 MAC) inhalation dose-dependently inhibited the nociceptive transmission in spinal cord dorsal horn. On the other hand, desflurane(DES)inhalation at anesthetic concentration(>0.5MAC) had similar effect as SEV, however, DES inhalation at subanesthetic concentration(<0.2MAC) paradoxically enhanced the nociceptive synaptic transmission. Both volatile anesthetics affected on the release of excitatory neurotransmitters from primary afferent fiber terminals, whereas　they had little impact on the inhibitory synaptic transmission. Intravenous propofol had no significant effect on pain modulation. The behavioral test by thermal/cold stimulation also revealed the hyperalgesic property by DES at subanesthetic concentration.