Chronic pain treatment strategy targeting PACAP-PAC1-induced astrocyte signaling

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462384
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kagoshima University
• Principal Investigator: Ohnou Tetsuya 鹿児島大学, 医歯学域附属病院, 助教 (60457661)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: PACAP / PAC1 / アストロサイト / JNK / 慢性痛

Outline of Final Research Achievements

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in the spinal dorsal horn and dorsal root ganglia, and markedly upregulated in peripheral nerve injury or inflammation, suggesting an important role in the modulation of spinal nociceptive transmission. However, the involvement of PACAP type 1 (PAC1) receptor and its downstream signaling mechanism have not been clarified yet. We found that a single intrathecal injection of PACAP or maxadilan (a PAC1 receptor agonist) produced long-lasting mechanical allodynia, and the spinal PAC1 receptor stimulation also caused sustained astrocytic activation. Our data suggest that the interaction between dorsal horn neurons and astrocytes evoked by PAC1 receptor-mediated signal transduction is critically involved in the induction and maintenance of the long-lasting mechanical allodynia. The signaling pathway linking between PAC1 receptor stimulation and astroglial activation may offer a new opportunity to treat chronic pain.

Free Research Field

疼痛