Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis
<p>Abstract</p> <p>Background</p> <p>Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-08-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://www.jbiomedsci.com/content/19/1/77 |
| _version_ | 1818154967394942976 |
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| author | Izumi Masashi Ikeuchi Masahiko Ji Qinghui Tani Toshikazu |
| author_facet | Izumi Masashi Ikeuchi Masahiko Ji Qinghui Tani Toshikazu |
| author_sort | Izumi Masashi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.</p> <p>Methods</p> <p>We induced OA <it>via</it> intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.</p> <p>Results</p> <p>OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.</p> <p>Conclusions</p> <p>Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.</p> |
| first_indexed | 2024-12-11T14:34:55Z |
| format | Article |
| id | doaj.art-7aa29e0dc0314e769bde24489406107f |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-11T14:34:55Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-7aa29e0dc0314e769bde24489406107f2022-12-22T01:02:14ZengBMCJournal of Biomedical Science1021-77701423-01272012-08-011917710.1186/1423-0127-19-77Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritisIzumi MasashiIkeuchi MasahikoJi QinghuiTani Toshikazu<p>Abstract</p> <p>Background</p> <p>Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.</p> <p>Methods</p> <p>We induced OA <it>via</it> intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.</p> <p>Results</p> <p>OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.</p> <p>Conclusions</p> <p>Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.</p>http://www.jbiomedsci.com/content/19/1/77OsteoarthritisAcid sensing ion channel (ASIC)PainAPETx2JointInflammation |
| spellingShingle | Izumi Masashi Ikeuchi Masahiko Ji Qinghui Tani Toshikazu Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis Journal of Biomedical Science Osteoarthritis Acid sensing ion channel (ASIC) Pain APETx2 Joint Inflammation |
| title | Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis |
| title_full | Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis |
| title_fullStr | Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis |
| title_full_unstemmed | Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis |
| title_short | Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis |
| title_sort | local asic3 modulates pain and disease progression in a rat model of osteoarthritis |
| topic | Osteoarthritis Acid sensing ion channel (ASIC) Pain APETx2 Joint Inflammation |
| url | http://www.jbiomedsci.com/content/19/1/77 |
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