TY - JOUR
T1 - The pivotal role played by lipocalin-2 in chronic inflammatory pain
AU - Jha, Mithilesh Kumar
AU - Jeon, Sangmin
AU - Jin, Myungwon
AU - Ock, Jiyeon
AU - Kim, Jong Heon
AU - Lee, Won Ha
AU - Suk, Kyoungho
N1 - Funding Information:
This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( A111345 ), and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2008-0062282 and 2012M3A9B6055414 ).
PY - 2014/4
Y1 - 2014/4
N2 - Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12. h after CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2 and its receptor 24p3R were mainly expressed in infiltrating neutrophils and macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were significantly diminished in Lcn2-deficient mice compared to wild-type animals. Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naïve mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.
AB - Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12. h after CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2 and its receptor 24p3R were mainly expressed in infiltrating neutrophils and macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were significantly diminished in Lcn2-deficient mice compared to wild-type animals. Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naïve mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.
KW - Chronic inflammatory pain
KW - Glia
KW - Hindpaw
KW - Inflammation
KW - Lipocalin-2
KW - Macrophage
KW - Neutrophil
KW - Proalgesic mediators
KW - Spinal cord
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U2 - 10.1016/j.expneurol.2014.01.009
DO - 10.1016/j.expneurol.2014.01.009
M3 - Article
C2 - 24440229
AN - SCOPUS:84893404407
SN - 0014-4886
VL - 254
SP - 41
EP - 53
JO - Experimental Neurology
JF - Experimental Neurology
ER -