Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

Journal of Biomedical Science

Research

Toshikazu Tani¹  Masashi Izumi¹  Qinghui Ji¹  Masahiko Ikeuchi¹ 

[1] Department of Orthopaedic Surgery, Kochi University, 783-8505, Oko-cho Kohasu, Nankoku, Japan;

关键词: Osteoarthritis;    Acid sensing ion channel (ASIC);    Pain;    APETx2;    Joint;    Inflammation;   

DOI  :  10.1186/1423-0127-19-77

 received in 2011-12-18, accepted in 2012-08-16,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundRecent 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.MethodsWe induced OA via 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.ResultsOA 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.ConclusionsLocal 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.

【 授权许可】

Unknown   
© Izumi et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.