The pathomechanism of chronic low back pain through CGRP signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16700
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kitasato University
• Principal Investigator: Miyagi Masayuki 北里大学, 医学部, 講師 (90627556)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 椎間板性腰痛 / カルシトニン遺伝子関連ペプチド / 神経成長因子

Outline of Final Research Achievements

CGRP and NGF could contribute to pain in several musculoskeletal disorders. We examined M1 and M2 macrophage markers, CGRP and NGF and cytokine expression in IVD-derived cells from control and IVD-injured mice for 28 days following injury. Ngf mRNA expression was increased 1 day after injury in injured compared to control mice, and persisted for up to 28 days. Flow cytometric analysis demonstrated that the proportion of F4/80+CD11b+ cells was significantly increased from 1 day after injury for up to 28 days.TNF-α and TGF-β stimulated Ngf mRNA and NGF protein expression in IVD cells. Our results suggest that TNF-α and TGF-β may stimulate NGF production under inflammatory and non-inflammatory conditions following IVD injury. As TNF-α and TGF-β are produced by M1 and M2 macrophages, further investigations are needed to reveal the role of macrophages in NGF expression following IVD injury. Our results may aid in developing treatments for IVD-related LBP pathology.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

腰痛の生涯罹患率は85％と報告され、超高齢者社会を迎えた我が国における腰痛患者は2,800万人にものぼる。本邦の厚生労働省の報告では腰痛は男性１位、女性２位にランクされる重大な国民愁訴である。多大な医療費がこの腰痛疼痛治療に費やされているのが現状であり、腰痛による経済損失は年間7,000億円と推定されている。本研究成果に基づいた更なる腰痛機序の解明と治療法の開発は社会・医療経済的にも重要な意義を持つ。