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

Ichiro Takasaki; Koji Nakamura; Ayaka Shimodaira; Ai Watanabe; Huy Du Nguyen; Takuya Okada; Naoki Toyooka; Atsuro Miyata; Takashi Kurihara

doi:10.1016/j.jphs.2018.11.011

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

Ichiro Takasaki^*, Koji Nakamura, Ayaka Shimodaira, Ai Watanabe, Huy Du Nguyen, Takuya Okada, Naoki Toyooka, Atsuro Miyata, Takashi Kurihara

^*Corresponding author for this work

Life Sciences and Bioengineering

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English
Pages (from-to)	129-132
Number of pages	4
Journal	Journal of Pharmacological Sciences
Volume	139
Issue number	2
DOIs	https://doi.org/10.1016/j.jphs.2018.11.011
State	Published - 2019/02

Keywords

Inflammatory pain
PACAP type 1 (PAC1) receptor
Small-molecule antagonist

ASJC Scopus subject areas

Molecular Medicine
Pharmacology

Access to Document

10.1016/j.jphs.2018.11.011

Cite this

@article{8a480ef157144aeca33b737a71f39196,

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

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",

author = "Ichiro Takasaki and Koji Nakamura and Ayaka Shimodaira and Ai Watanabe and {Du Nguyen}, Huy and Takuya Okada and Naoki Toyooka and Atsuro Miyata and Takashi Kurihara",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2019",

month = feb,

doi = "10.1016/j.jphs.2018.11.011",

language = "英語",

volume = "139",

pages = "129--132",

journal = "Journal of Pharmacological Sciences",

issn = "1347-8613",

publisher = "Japanese Pharmacological Society",

number = "2",

}

TY - JOUR

T1 - The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice

AU - Takasaki, Ichiro

AU - Nakamura, Koji

AU - Shimodaira, Ayaka

AU - Watanabe, Ai

AU - Du Nguyen, Huy

AU - Okada, Takuya

AU - Toyooka, Naoki

AU - Miyata, Atsuro

AU - Kurihara, Takashi

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

KW - Inflammatory pain

KW - PACAP type 1 (PAC1) receptor

KW - Small-molecule antagonist

UR - http://www.scopus.com/inward/record.url?scp=85058186755&partnerID=8YFLogxK

U2 - 10.1016/j.jphs.2018.11.011

DO - 10.1016/j.jphs.2018.11.011

M3 - 学術論文

C2 - 30552012

AN - SCOPUS:85058186755

SN - 1347-8613

VL - 139

SP - 129

EP - 132

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this