The role of gonadal steroid hormones in pain responses of CRH neurons in the BSTDL

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Hagiwara Hiroko 聖マリアンナ医科大学, 医学部, 助教 (90468207)
• Co-Investigator(Kenkyū-buntansha): 福島 篤 聖マリアンナ医科大学, 医学部, 講師 (10442716)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 疼痛 / 性差 / 分界条床核 / formalin test

Outline of Final Research Achievements

We found that the dorsolateral subdivision of the bed nucleus of the stria terminalis (BSTDL) plays a role in controlling pain response. We studied the electrophysiological properties of Corticotropin-releaseing hormone (CRH) neurons of the BSTDL in mice with a yellow fluorescent protein under the control of the CRH promoter. Whole-cell patch-clamp recordings were performed to analyze miniature excitatory postsynaptic currents (mEPSC) in CRH neurons in the BSTDL slices. The voltage clamp analysis revealed that the frequency of mEPSC was increased by formalin injection in female mice but not in male mice. In gonadalectomized male and female mice, low concentration estrogen tube (E2) was replaced subcutaneously and similar experiments were performed. In female mice but not in male mice, the frequency of mEPSC was increased by E2 implantation. The present study suggests that the sex difference in pain responses may be mediated by estrogen sensitivity of CRH neurons in the BSTDL.

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

これまでの痛み研究は脊髄レベルでの研究が多く報告されていた。近年、痛みの情動成分の重要性が報告されているが、情動には多様な側面があり研究は困難であった。一方、女性の痛みに対する高い脆弱性の基盤や、情動における中枢神経系内メカニズムに関する研究は少ない。本研究は、情動が痛みを調節するメカニズムについて性差に着目し、BSTLにおけるCRHニューロンをターゲットに分子基盤と行動発現がどのように作用しているかを明らかした先駆的な研究である。