Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model
Abstract Background Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destru...
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doaj-d2f8e1df135e4b248f9d99d386c051042020-11-25T02:14:16ZengBMCArthritis Research & Therapy1478-63622019-02-0121111110.1186/s13075-019-1819-9Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat modelAnna Katri0Aneta Dąbrowska1Henrik Löfvall2Ming Ding3Morten A. Karsdal4Kim V. Andreassen5Christian S. Thudium6Kim Henriksen7Department of Drug Design and Pharmacology, University of CopenhagenBiomarkers and Research, Nordic BioscienceBiomarkers and Research, Nordic BioscienceDepartment of Orthopaedics and Traumatology, Institute of Clinical Research, Odense University Hospital, University of Southern DenmarkBiomarkers and Research, Nordic BioscienceBiomarkers and Research, Nordic BioscienceBiomarkers and Research, Nordic BioscienceBiomarkers and Research, Nordic BioscienceAbstract Background Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA. Methods Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography. Results Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed. Conclusions This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.http://link.springer.com/article/10.1186/s13075-019-1819-9Rheumatoid arthritisCIADACRANSAIDsPainBone |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Katri Aneta Dąbrowska Henrik Löfvall Ming Ding Morten A. Karsdal Kim V. Andreassen Christian S. Thudium Kim Henriksen |
spellingShingle |
Anna Katri Aneta Dąbrowska Henrik Löfvall Ming Ding Morten A. Karsdal Kim V. Andreassen Christian S. Thudium Kim Henriksen Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model Arthritis Research & Therapy Rheumatoid arthritis CIA DACRA NSAIDs Pain Bone |
author_facet |
Anna Katri Aneta Dąbrowska Henrik Löfvall Ming Ding Morten A. Karsdal Kim V. Andreassen Christian S. Thudium Kim Henriksen |
author_sort |
Anna Katri |
title |
Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
title_short |
Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
title_full |
Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
title_fullStr |
Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
title_full_unstemmed |
Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
title_sort |
combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2019-02-01 |
description |
Abstract Background Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA. Methods Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography. Results Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed. Conclusions This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure. |
topic |
Rheumatoid arthritis CIA DACRA NSAIDs Pain Bone |
url |
http://link.springer.com/article/10.1186/s13075-019-1819-9 |
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