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Published on: November 15, 2024
The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice
Ichiro Takasaki1, Koji Nakamura2, Ayaka Shimodaira2
1Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan; Graduate School of Innovative Life Sciences, University of Toyama, Toyama, Japan.
Abstract:
We recently developed PA-8, a novel small-molecule antagonist of PACAP type 1 (PAC1) receptor. In the present study, we examined whether PA-8 was effective against formalin-induced inflammatory pain in mice. Both intrathecal and oral administration of PA-8 resulted in the dose-dependent attenuation of the second phase of formalin-induced nociceptive responses. PA-8 also inhibited c-fos upregulation in the ipsilateral dorsal horn of the spinal cord. The results suggested that PACAP-PAC1 receptor signaling system in the spinal cord were primarily involved in the transmission of inflammatory pain, and PA-8 could be useful for the development of novel analgesics for treating inflammatory pain.
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