Elucidating the Relevance of Pathological Chronic Pain and Hypoxic Response

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18252
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Keio University
• Principal Investigator: TORAMARU Tomoko 慶應義塾大学, 医学部(信濃町), 助教 (70594612)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 麻酔学 / 低酸素応答 / プレコンディショニング / 慢性痛 / 複合性局所疼痛症候群

Outline of Final Research Achievements

The involvement of hypoxic response mechanisms in the local functional impairments in surgical wounds is unclear. This study characterised the tissue hypoxia in the surgical wound and investigated the role of prolyl hydroxylase domain enzymes (PHD) inhibitor, on postoperative local functional impairments in a murine model of deep hind paw incision.
Prominent tissue hypoxia was detected within axons in nerve bundles underneath the wounds. Perioperative PHD inhibition failed to ease spontaneous pain-like behaviors but it mitigated local sudomotor impairment after surgery. Upregulation of sympathetic innervation in eccrine glands was observed in the PHD inhibitied skins in accordance with the in vitro study where PHD inhibition promoted neurite growth of PC12 cells.These results suggest a possible involvement of hypoxic response mechanisms in the progression of postoperative functional impairments such as local sudomotor dysfunction, via regulation of sympathetic innervation.

Free Research Field

麻酔学

Academic Significance and Societal Importance of the Research Achievements

本研究は、マウス術後痛モデルの創部神経束においてPHDが存在することを突き止めた。PHD阻害は術後痛には影響なかったものの、術後局所発汗障害を改善した。PHD阻害は、交感神経保護作用を有し、予防的なPHD阻害が術後自律神経障害に対し保護的に働く可能性が示唆された。
創部の強い痛みや自律神経障害が慢性的に続く複合性局所疼痛症候群 (Complex regional pain syndrome: CRPS) では、術後創部における虚血が発症の一因とされている。CRPS患者の病理組織は本研究での知見に合致する点が見受けられ、PHD阻害が術後CRPSへの進展を予防する可能性も示唆された。