title: TDAG8 involved in initiating inflammatory hyperalgesia and establishing hyperalgesic priming in mice.
abstract: Chronic pain, resulting from injury, arthritis, and cancer, is often accompanied by inflammation. High concentrations of protons found in inflamed tissues results in tissue acidosis, a major cause of pain and hyperalgesia. Acidosis signals may mediate a transition from acute to chronic hyperalgesia (hyperalgesic priming) via proton-sensing G-protein-coupled receptors (GPCRs). The expression of T-cell death-associated gene 8 (TDAG8), a proton-sensing GPCR, is increased during inflammatory hyperalgesia. Attenuating TDAG8 expression in the spinal cord inhibits bone cancer pain, but whether TDAG8 is involved in inflammatory hyperalgesia or hyperalgesic priming remains unclear. In this study, we used TDAG8-knockout or -knockdown to explore the role of TDAG8 in pain. Suppressed TDAG8 expression delayed the onset of inflammatory hyperalgesia and shortened hyperalgesic time in mice. In a dual acid-injection model (acid [pH 5.0] injected twice, 5 days apart), shRNA inhibition of TDAG8 shortened the duration of the second hyperalgesia. Similar results were found in TDAG8-deficient mice. The dual administration of TDAG8 agonist also confirmed that TDAG8 is involved in hyperalgsic priming. Accordingly, TDAG8 may mediate acidosis signals to initiate inflammatory hyperalgesia and establish hyperalgesic priming.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Dai
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Wei-Shan
authors.initials: WS
authors.lastname: Hsieh
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Immunology, Graduate School of Medicine, Akita University, Akita city, Japan.
authors.forename: Satoshii
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan City, Taiwan.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Sun
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002351:Carrageenan; D000242:Cyclic AMP / Q000378:metabolism; D005620:Freund's Adjuvant; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D042541:Intracellular Space / Q000378:metabolism; D008813:Mice, Inbred ICR; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: C513337:GPR65 protein, mouse; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D002351:Carrageenan; D005620:Freund's Adjuvant; D000242:Cyclic AMP; D002118:Calcium