The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice

  • J Pharmacol Sci. 2019 Feb;139(2):129-132. doi: 10.1016/j.jphs.2018.11.011.
Ichiro Takasaki  1 ,  Koji Nakamura  2 ,  Ayaka Shimodaira  2 ,  Ai Watanabe  2 ,  Huy Du Nguyen  3 ,  Takuya Okada  3 ,  Naoki Toyooka  3 ,  Atsuro Miyata  4 ,  Takashi Kurihara  4
Affiliations
  • 1. Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan; Graduate School of Innovative Life Sciences, University of Toyama, Toyama, Japan. Electronic address: [email protected].
  • 2. Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan.
  • 3. Graduate School of Innovative Life Sciences, University of Toyama, Toyama, Japan; 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.
PMID: 30552012 DOI: 10.1016/j.jphs.2018.11.011
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
Inflammatory pain; PACAP type 1 (PAC1) receptor; Small-molecule antagonist.
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