Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome
Complex regional pain syndrome (CRPS) is an intractable chronic pain syndrome with various signs and symptoms including allodynia/hyperalgesia, edema, swelling, and skin abnormalities. However, a definitive therapeutic treatment for CRPS has not been established. In CRPS patients, inflammatory cytok...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
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| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786132300035X |
| _version_ | 1797769813901180928 |
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| author | Shiho Shibata Hideaki Tagashira Takayuki Nemoto Satomi Kita Tomo Kita Yasuharu Shinoda Kouzaburo Akiyoshi Ken Yamaura Takahiro Iwamoto |
| author_facet | Shiho Shibata Hideaki Tagashira Takayuki Nemoto Satomi Kita Tomo Kita Yasuharu Shinoda Kouzaburo Akiyoshi Ken Yamaura Takahiro Iwamoto |
| author_sort | Shiho Shibata |
| collection | DOAJ |
| description | Complex regional pain syndrome (CRPS) is an intractable chronic pain syndrome with various signs and symptoms including allodynia/hyperalgesia, edema, swelling, and skin abnormalities. However, a definitive therapeutic treatment for CRPS has not been established. In CRPS patients, inflammatory cytokines such as TNF-α and IL-1β have been shown to increase in affected areas, suggesting that these molecules may be potential therapeutic targets for CRPS. Here, we first created a novel CRPS mouse model (CRPS-II-like) via sciatic nerve injury and cast immobilization, which was characterized by mechanical allodynia, local edema, and skin abnormalities, to evaluate the pathophysiology and pharmacotherapy of CRPS. When an anti-TNF-α antibody was consecutively administered near the injured sciatic nerve of CRPS model mice, persistent allodynia and CRPS-related signs in the ipsilateral hindpaw were markedly attenuated to control levels. Perineural administration of anti-TNF-α antibody also suppressed the upregulation of inflammatory cytokines as well as the activation of macrophages and Schwann cells in the injured sciatic nerve. These findings indicate that persistent allodynia and CRPS-related signs in CRPS models are primarily associated with TNF-α-mediated immune responses in injured peripheral nerves, suggesting that perineural treatment with anti-TNF-α antibody might be therapeutically useful. |
| first_indexed | 2024-03-12T21:14:27Z |
| format | Article |
| id | doaj.art-f27089d75bbf4529a4d8ba03072f0a0d |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-03-12T21:14:27Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-f27089d75bbf4529a4d8ba03072f0a0d2023-07-30T04:21:58ZengElsevierJournal of Pharmacological Sciences1347-86132023-09-011531111Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndromeShiho Shibata0Hideaki Tagashira1Takayuki Nemoto2Satomi Kita3Tomo Kita4Yasuharu Shinoda5Kouzaburo Akiyoshi6Ken Yamaura7Takahiro Iwamoto8Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Anesthesiology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Corresponding author. Department of Pharmacology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Anesthesiology, Faculty of Medicine, Fukuoka University, Fukuoka, JapanDepartment of Anesthesiology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Anesthesiology & Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Corresponding author. Department of Pharmacology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.Complex regional pain syndrome (CRPS) is an intractable chronic pain syndrome with various signs and symptoms including allodynia/hyperalgesia, edema, swelling, and skin abnormalities. However, a definitive therapeutic treatment for CRPS has not been established. In CRPS patients, inflammatory cytokines such as TNF-α and IL-1β have been shown to increase in affected areas, suggesting that these molecules may be potential therapeutic targets for CRPS. Here, we first created a novel CRPS mouse model (CRPS-II-like) via sciatic nerve injury and cast immobilization, which was characterized by mechanical allodynia, local edema, and skin abnormalities, to evaluate the pathophysiology and pharmacotherapy of CRPS. When an anti-TNF-α antibody was consecutively administered near the injured sciatic nerve of CRPS model mice, persistent allodynia and CRPS-related signs in the ipsilateral hindpaw were markedly attenuated to control levels. Perineural administration of anti-TNF-α antibody also suppressed the upregulation of inflammatory cytokines as well as the activation of macrophages and Schwann cells in the injured sciatic nerve. These findings indicate that persistent allodynia and CRPS-related signs in CRPS models are primarily associated with TNF-α-mediated immune responses in injured peripheral nerves, suggesting that perineural treatment with anti-TNF-α antibody might be therapeutically useful.http://www.sciencedirect.com/science/article/pii/S134786132300035XComplex regional pain syndromeAnti-TNF-α antibodyMechanical allodyniaEdemaSciatic nerve |
| spellingShingle | Shiho Shibata Hideaki Tagashira Takayuki Nemoto Satomi Kita Tomo Kita Yasuharu Shinoda Kouzaburo Akiyoshi Ken Yamaura Takahiro Iwamoto Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome Journal of Pharmacological Sciences Complex regional pain syndrome Anti-TNF-α antibody Mechanical allodynia Edema Sciatic nerve |
| title | Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| title_full | Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| title_fullStr | Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| title_full_unstemmed | Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| title_short | Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| title_sort | perineural treatment with anti tnf α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome |
| topic | Complex regional pain syndrome Anti-TNF-α antibody Mechanical allodynia Edema Sciatic nerve |
| url | http://www.sciencedirect.com/science/article/pii/S134786132300035X |
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