Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models
Prostaglandin E2 (PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2 synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/9847840 |
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| _version_ | 1832559975952547840 |
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| author | Ryusuke Sugita Harumi Kuwabara Kazufumi Kubota Kotaro Sugimoto Toshihiro Kiho Atsushi Tengeiji Katsuhiro Kawakami Kohei Shimada |
| author_facet | Ryusuke Sugita Harumi Kuwabara Kazufumi Kubota Kotaro Sugimoto Toshihiro Kiho Atsushi Tengeiji Katsuhiro Kawakami Kohei Shimada |
| author_sort | Ryusuke Sugita |
| collection | DOAJ |
| description | Prostaglandin E2 (PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2 synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin-4-yl]carbonyl amino)cyclohexyl] propanoic acid, in rat yeast-induced acute and adjuvant-induced chronic inflammatory pain models. Although this compound suppressed the synthesis of PGE2 selectively, no analgesic effect was shown in both inflammatory pain models. Prostacyclin (PGI2) also plays crucial roles in inflammatory pain, so we evaluated the involvement of PGI2 signaling in rat inflammatory pain models using prostacyclin receptor (IP) antagonist, RO3244019. RO3244019 showed no analgesic effect in inflammatory pain models, but concomitant administration of compound I and RO3244019 showed analgesic effects comparable to celecoxib, a specific cyclooxygenase- (COX-) 2 inhibitor. Furthermore, coadministration of PGE2 receptor 4 (EP4) antagonist, CJ-023423, and RO3244019 also showed an analgesic effect. These findings suggest that both PGE2 signaling, especially through the EP4 receptor, and PGI2 signaling play critical roles in inflammatory pain and concurrent inhibition of both signals is important for suppression of inflammatory hyperalgesia. |
| format | Article |
| id | doaj-art-675a55b2ab26412da50e75fde9b2f721 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-675a55b2ab26412da50e75fde9b2f7212025-02-03T01:28:49ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/98478409847840Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain ModelsRyusuke Sugita0Harumi Kuwabara1Kazufumi Kubota2Kotaro Sugimoto3Toshihiro Kiho4Atsushi Tengeiji5Katsuhiro Kawakami6Kohei Shimada7Cardiovascular-Metabolics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanFrontier Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanBiological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanFrontier Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanMedicinal Chemistry Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanVenture Science Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanGlobal Project Management Department, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanFrontier Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanProstaglandin E2 (PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2 synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin-4-yl]carbonyl amino)cyclohexyl] propanoic acid, in rat yeast-induced acute and adjuvant-induced chronic inflammatory pain models. Although this compound suppressed the synthesis of PGE2 selectively, no analgesic effect was shown in both inflammatory pain models. Prostacyclin (PGI2) also plays crucial roles in inflammatory pain, so we evaluated the involvement of PGI2 signaling in rat inflammatory pain models using prostacyclin receptor (IP) antagonist, RO3244019. RO3244019 showed no analgesic effect in inflammatory pain models, but concomitant administration of compound I and RO3244019 showed analgesic effects comparable to celecoxib, a specific cyclooxygenase- (COX-) 2 inhibitor. Furthermore, coadministration of PGE2 receptor 4 (EP4) antagonist, CJ-023423, and RO3244019 also showed an analgesic effect. These findings suggest that both PGE2 signaling, especially through the EP4 receptor, and PGI2 signaling play critical roles in inflammatory pain and concurrent inhibition of both signals is important for suppression of inflammatory hyperalgesia.http://dx.doi.org/10.1155/2016/9847840 |
| spellingShingle | Ryusuke Sugita Harumi Kuwabara Kazufumi Kubota Kotaro Sugimoto Toshihiro Kiho Atsushi Tengeiji Katsuhiro Kawakami Kohei Shimada Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models Mediators of Inflammation |
| title | Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models |
| title_full | Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models |
| title_fullStr | Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models |
| title_full_unstemmed | Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models |
| title_short | Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models |
| title_sort | simultaneous inhibition of pge2 and pgi2 signals is necessary to suppress hyperalgesia in rat inflammatory pain models |
| url | http://dx.doi.org/10.1155/2016/9847840 |
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