The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain
Chronic pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs) is a major problem and drugs for such pain are needed. Many studies suggest that transient receptor potential vanilloid type 1 (TRPV1) is associated with NSAID-refractory chronic pain. Therefore, we investigated the involvemen...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319303305 |
| _version_ | 1811288193989869568 |
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| author | Yoshihiro Kitagawa Isao Tamai Yuji Hamada Kenji Usui Masashi Wada Masahiro Sakata Mutsuyoshi Matsushita |
| author_facet | Yoshihiro Kitagawa Isao Tamai Yuji Hamada Kenji Usui Masashi Wada Masahiro Sakata Mutsuyoshi Matsushita |
| author_sort | Yoshihiro Kitagawa |
| collection | DOAJ |
| description | Chronic pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs) is a major problem and drugs for such pain are needed. Many studies suggest that transient receptor potential vanilloid type 1 (TRPV1) is associated with NSAID-refractory chronic pain. Therefore, we investigated the involvement of TRPV1 in NSAID-refractory chronic pain using experimental models for NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. The selective TRPV1 antagonist JTS-653 {(3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide} reversed mechanical hyperalgesia on day 7 after injection of complete-Freund-adjuvant into the hindpaw in rats at 0.3 mg/kg, whereas indomethacin showed no effect. JTS-653 reduced chronic pain at 0.3 mg/kg in herpes simplex virus-1–inoculated mice that has been reported as NSAID-refractory pain. JTS-653 partially attenuated mechanical hyperalgesia in the L5 spinal nerve ligation model in rats at 0.3 mg/kg, whereas indomethacin showed no effect. Both JTS-653 and indomethacin reduced formalin-induced pain in the second phase, whereas they showed no effect in the first phase. JTS-653 did not affect the nociception of noxious thermal and mechanical stimuli and motor coordination in normal rats. These findings demonstrate the TRPV1 involvement in NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. TRPV1 antagonists would be useful for the treatment of NSAID-refractory chronic pain. Keywords:: transient receptor potential vanilloid type 1 (TRPV1), non-steroidal anti-inflammatory drug (NSAID), chronic pain, post-herpetic pain, herpes simplex virus-1 (HSV-1) |
| first_indexed | 2024-04-13T03:32:44Z |
| format | Article |
| id | doaj.art-808d9597bbef435b96b6195db3d29e12 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-13T03:32:44Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-808d9597bbef435b96b6195db3d29e122022-12-22T03:04:25ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-011222128137The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic PainYoshihiro Kitagawa0Isao Tamai1Yuji Hamada2Kenji Usui3Masashi Wada4Masahiro Sakata5Mutsuyoshi Matsushita6Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan; Corresponding author. yoshihiro.kitagawa@jt.comCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanCentral Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, JapanChronic pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs) is a major problem and drugs for such pain are needed. Many studies suggest that transient receptor potential vanilloid type 1 (TRPV1) is associated with NSAID-refractory chronic pain. Therefore, we investigated the involvement of TRPV1 in NSAID-refractory chronic pain using experimental models for NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. The selective TRPV1 antagonist JTS-653 {(3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide} reversed mechanical hyperalgesia on day 7 after injection of complete-Freund-adjuvant into the hindpaw in rats at 0.3 mg/kg, whereas indomethacin showed no effect. JTS-653 reduced chronic pain at 0.3 mg/kg in herpes simplex virus-1–inoculated mice that has been reported as NSAID-refractory pain. JTS-653 partially attenuated mechanical hyperalgesia in the L5 spinal nerve ligation model in rats at 0.3 mg/kg, whereas indomethacin showed no effect. Both JTS-653 and indomethacin reduced formalin-induced pain in the second phase, whereas they showed no effect in the first phase. JTS-653 did not affect the nociception of noxious thermal and mechanical stimuli and motor coordination in normal rats. These findings demonstrate the TRPV1 involvement in NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. TRPV1 antagonists would be useful for the treatment of NSAID-refractory chronic pain. Keywords:: transient receptor potential vanilloid type 1 (TRPV1), non-steroidal anti-inflammatory drug (NSAID), chronic pain, post-herpetic pain, herpes simplex virus-1 (HSV-1)http://www.sciencedirect.com/science/article/pii/S1347861319303305 |
| spellingShingle | Yoshihiro Kitagawa Isao Tamai Yuji Hamada Kenji Usui Masashi Wada Masahiro Sakata Mutsuyoshi Matsushita The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain Journal of Pharmacological Sciences |
| title | The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain |
| title_full | The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain |
| title_fullStr | The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain |
| title_full_unstemmed | The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain |
| title_short | The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain |
| title_sort | orally administered selective trpv1 antagonist jts 653 attenuates chronic pain refractory to non steroidal anti inflammatory drugs in rats and mice including post herpetic pain |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319303305 |
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