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

@article{citeulike:3857159, 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.}, author = {Yen, Yi T. and Tu, Pan H. and Chen, Chien J. and Lin, Yi W. and Hsieh, Sung T. and Chen, Chih C.}, citeulike-article-id = {3857159}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1744-8069-5-1}, doi = {10.1186/1744-8069-5-1}, issn = {1744-8069}, journal = {Molecular Pain}, keywords = {asic3, inflammation, pain, sub\_acute\_phase\_inflammation}, number = {1}, posted-at = {2009-01-07 13:19:22}, priority = {3}, title = {Role of acid-sensing ion channel 3 in sub-acute-phase inflammation}, url = {http://dx.doi.org/10.1186/1744-8069-5-1}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:3857159 L3 - citeulike-article-id:3857159 N2 - 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. IS - 1 JF - Molecular Pain SN - 1744-8069 TI - Role of acid-sensing ion channel 3 in sub-acute-phase inflammation VL - 5 KW - asic3 KW - inflammation KW - pain KW - sub_acute_phase_inflammation AU - Yen, Yi AU - Tu, Pan AU - Chen, Chien AU - Lin, Yi AU - Hsieh, Sung AU - Chen, Chih PY - 2009/// UR - http://dx.doi.org/10.1186/1744-8069-5-1 ER -