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Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice.
PLoS One. 2016; 11(11):e0165200.Plos

Abstract

Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment.

Authors+Show Affiliations

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China.Department of Laboratory and Equipment Administration, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China. Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, United States of America.Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, United States of America.Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, United States of America.Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America.Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China.Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China.Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27812120

Citation

Liu, Boyi, et al. "Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice." PloS One, vol. 11, no. 11, 2016, pp. e0165200.
Liu B, Tai Y, Caceres AI, et al. Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice. PLoS One. 2016;11(11):e0165200.
Liu, B., Tai, Y., Caceres, A. I., Achanta, S., Balakrishna, S., Shao, X., Fang, J., & Jordt, S. E. (2016). Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice. PloS One, 11(11), e0165200. https://doi.org/10.1371/journal.pone.0165200
Liu B, et al. Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice. PLoS One. 2016;11(11):e0165200. PubMed PMID: 27812120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice. AU - Liu,Boyi, AU - Tai,Yan, AU - Caceres,Ana I, AU - Achanta,Satyanarayana, AU - Balakrishna,Shrilatha, AU - Shao,Xiaomei, AU - Fang,Junfan, AU - Jordt,Sven-Eric, Y1 - 2016/11/03/ PY - 2016/06/03/received PY - 2016/10/07/accepted PY - 2016/11/5/pubmed PY - 2017/7/4/medline PY - 2016/11/5/entrez SP - e0165200 EP - e0165200 JF - PloS one JO - PLoS One VL - 11 IS - 11 N2 - Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27812120/Oxidized_Phospholipid_OxPAPC_Activates_TRPA1_and_Contributes_to_Chronic_Inflammatory_Pain_in_Mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0165200 DB - PRIME DP - Unbound Medicine ER -