Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception

In this study, we investigated the mechanisms underlying carrageenan-induced chronic pain and the therapeutic effect of the anti-inflammatory drug meloxicam. Rats were injected with 3 % carrageenan into the masseter muscle. These rats exhibited acute and chronic hypersensitivity to mechanical stimul...

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Main Authors: Toru Yamamoto, Mitsuhiro Yoshida, Yuhei Koyama, Yatendra Mulpuri, Eiji Imado, Kana Oue, Mitsuru Doi, Yoshitaka Shimizu, Naotaka Kishimoto, Hiroshi Hanamoto, Kenji Seo
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Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024176335
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author Toru Yamamoto
Mitsuhiro Yoshida
Yuhei Koyama
Yatendra Mulpuri
Eiji Imado
Kana Oue
Mitsuru Doi
Yoshitaka Shimizu
Naotaka Kishimoto
Hiroshi Hanamoto
Kenji Seo
author_facet Toru Yamamoto
Mitsuhiro Yoshida
Yuhei Koyama
Yatendra Mulpuri
Eiji Imado
Kana Oue
Mitsuru Doi
Yoshitaka Shimizu
Naotaka Kishimoto
Hiroshi Hanamoto
Kenji Seo
author_sort Toru Yamamoto
collection DOAJ
description In this study, we investigated the mechanisms underlying carrageenan-induced chronic pain and the therapeutic effect of the anti-inflammatory drug meloxicam. Rats were injected with 3 % carrageenan into the masseter muscle. These rats exhibited acute and chronic hypersensitivity to mechanical stimuli for 6 weeks after injection. Pre-treatment with meloxicam prevented carrageenan-induced chronic hypersensitivity. Furthermore, minocycline and dexamethasone, but not acetaminophen, suppressed carrageenan-induced hypersensitivity in the chronic phase. Microglial reactivity in the trigeminal spinal subnucleus caudalis (Vc) was assessed by immunohistochemistry 3 days after treatment. The reactivity of microglial cells in the Vc was increased in carrageenan-treated rats compared with vehicle-injected rats. Meloxicam and dexamethasone, but not acetaminophen, prevented carrageenan-induced microglial hyperreactivity in the Vc. These results suggest that early prevention of peripheral/spinal inflammation suppresses microglial reactivity in the Vc and inhibits the development of orofacial chronic pain.
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spelling doaj-art-f0c4ae8a2a464dc2b56bc52b017091592025-02-02T05:27:52ZengElsevierHeliyon2405-84402025-01-01112e41602Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociceptionToru Yamamoto0Mitsuhiro Yoshida1Yuhei Koyama2Yatendra Mulpuri3Eiji Imado4Kana Oue5Mitsuru Doi6Yoshitaka Shimizu7Naotaka Kishimoto8Hiroshi Hanamoto9Kenji Seo10Division of Dental Anesthesiology, Faculty of Dentistry & Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, JapanDepartment of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, Japan; Corresponding author.Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, Tochigi, JapanTranslational Research Center, New York University College of Dentistry, New York, USADepartment of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, JapanDepartment of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, JapanDepartment of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDivision of Dental Anesthesiology, Faculty of Dentistry & Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, JapanDepartment of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDivision of Dental Anesthesiology, Faculty of Dentistry & Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, JapanIn this study, we investigated the mechanisms underlying carrageenan-induced chronic pain and the therapeutic effect of the anti-inflammatory drug meloxicam. Rats were injected with 3 % carrageenan into the masseter muscle. These rats exhibited acute and chronic hypersensitivity to mechanical stimuli for 6 weeks after injection. Pre-treatment with meloxicam prevented carrageenan-induced chronic hypersensitivity. Furthermore, minocycline and dexamethasone, but not acetaminophen, suppressed carrageenan-induced hypersensitivity in the chronic phase. Microglial reactivity in the trigeminal spinal subnucleus caudalis (Vc) was assessed by immunohistochemistry 3 days after treatment. The reactivity of microglial cells in the Vc was increased in carrageenan-treated rats compared with vehicle-injected rats. Meloxicam and dexamethasone, but not acetaminophen, prevented carrageenan-induced microglial hyperreactivity in the Vc. These results suggest that early prevention of peripheral/spinal inflammation suppresses microglial reactivity in the Vc and inhibits the development of orofacial chronic pain.http://www.sciencedirect.com/science/article/pii/S2405844024176335CarrageenanInflammationOrofacial chronic painMicrogliaTrigeminal spinal subnucleus caudalis
spellingShingle Toru Yamamoto
Mitsuhiro Yoshida
Yuhei Koyama
Yatendra Mulpuri
Eiji Imado
Kana Oue
Mitsuru Doi
Yoshitaka Shimizu
Naotaka Kishimoto
Hiroshi Hanamoto
Kenji Seo
Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
Heliyon
Carrageenan
Inflammation
Orofacial chronic pain
Microglia
Trigeminal spinal subnucleus caudalis
title Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
title_full Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
title_fullStr Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
title_full_unstemmed Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
title_short Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
title_sort early prevention of carrageenan induced peripheral spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception
topic Carrageenan
Inflammation
Orofacial chronic pain
Microglia
Trigeminal spinal subnucleus caudalis
url http://www.sciencedirect.com/science/article/pii/S2405844024176335
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