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The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice |
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| Authors: | Ichiro Takasaki Koji Nakamura Ayaka Shimodaira Ai Watanabe Huy Du Nguyen Takuya Okada Naoki Toyooka Atsuro Miyata Takashi Kurihara |
| Affiliation: | 1. Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan;2. Graduate School of Innovative Life Sciences, University of Toyama, Toyama, Japan;3. Department of Bio-functional Molecular Engineering, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan;4. Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 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. |
| Keywords: | PACAP type 1 (PAC1) receptor Small-molecule antagonist Inflammatory pain |
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