Critical roles of the chromogranin A-cathepsin B system in a transition of acute pain to a chronic pain state

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390416
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: HIROSHI Nakanishi 九州大学, 歯学研究科(研究院), 教授 (20155774)
• Co-Investigator(Kenkyū-buntansha): TAKE Hiro 九州大学, 歯学研究院, 准教授 (10420598) ; HAYASHI Yoshinori 九州大学, 歯学研究院, 助教 (80582717)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ミクログリア / カテプシンB / カテプシンS / クロモグラニンA / 炎症性疼痛 / 神経障害性疼痛

Outline of Final Research Achievements

In this study, we found that cathepsin B is an essential enzyme for the induction of chronic inflammatory pain through its activation of pro-caspase-1, which subsequently induces the maturation and secretion of IL-1β and IL-18 by spinal microglia. On the other hand, we found a peripheral pivotal role of cathepsin S in the development of neuropathic pain through the antigen-specific activation of CD4+ T-cells. After activation, CD4+ T-cells infiltrate into the dorsal spinal cord and secrete IFN-γ to reactivate microglia, which contribute to the transition of acute pain to a chronic pain state. Therefore, specific inhibitors for cathepsin B and cathepsin S may represent a useful new strategy for treating chronic pain.

Free Research Field

神経薬理学