Therapeutic mechanisms of chronic pain by dental pulp stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Nihon University (2019); Kyushu University (2016-2018)
• Principal Investigator: HAYASHI Yoshinori 日本大学, 歯学部, 助教 (80582717)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: カテプシンE / 好中球 / 一次求心性神経 / 慢性疼痛

Outline of Final Research Achievements

The effects of dental pulp stem cells on chronic pain was found to be suppression of immune cells accumulating in the cell bodies of primary afferent fibers which transmit nociceptive information from the peripheral tissue to the spinal dorsal horn. Neutrophils were accumulated in response to induction of chemokine (C-X-C motif) ligand 1 (CXCL1), a kind of chemokine, in dorsal root ganglion neurons. Adoptive transferred activated wild-type but not cathepsin E-deficient neutrophils elicited mechanical allodynia in naive mice. Pro-elastase was cleaved within neutrophils in a cathepsin E-dependent manner. Elastase released from neutrophils could cause facilitation of neuronal activity via protease activated receptor 2. Activation of neutrophils was mediated through toll-like receptor 4.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛は既存の鎮痛薬ですら効果が乏しい症状である。そのため，新たな鎮痛薬開発が望まれている。多くの研究が行われているにも関わらず，神経障害性疼痛のメカニズムおよび治療法は未だ十分に明らかにされていない。このような中，神経障害性疼痛の治療方法としての幹細胞の意義を提示することができた。また，免疫細胞を介したメカニズムも明らかにすることができた。これらの情報を基に，今後新たな治療方法の開発への応用に繋げることができる可能性を提示できたと考える。