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Molecular Pain

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Open Access 01-12-2009 | Research

Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

Authors: Yi-Tin Yen, Pan-Hsien Tu, Chien-Ju Chen, Yi-Wen Lin, Sung-Tsang Hsieh, Chih-Cheng Chen

Published in: Molecular Pain | Issue 1/2009

Abstract

Background

Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout (ASIC3^-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation.

Results

Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3^-/- mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3^+/+ controls, ASIC3^-/- mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3^-/- or ASIC3^+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3^-/- mice, as previously described. However, ASIC3^-/- mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3^+/+ mice.

Conclusion

We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.

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Title: Role of acid-sensing ion channel 3 in sub-acute-phase inflammation
Authors: Yi-Tin Yen
Pan-Hsien Tu
Chien-Ju Chen
Yi-Wen Lin
Sung-Tsang Hsieh
Chih-Cheng Chen
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-5-1

At a glance: The STEP trials

Springer Medicine

Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

Abstract

Background

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusion

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