title: Loss of ICA69 potentiates long-lasting hyperalgesia after subcutaneous formalin injection into the mouse hindpaw.
abstract: Islet-cell autoantigen 69 kDa (ICA69) plays an important role in many diseases and physiological activities by forming heteromeric complexes with protein interacts with C-kinase 1 (PICK1). PICK1 is critical for inflammatory pain hypersensitivity by regulating trafficking of AMPA receptor subunit GluA2 in spinal neurons. However, the role of ICA69 in inflammatory pain has not yet been investigated. Here we reported that expression of PICK1 in spinal cord was reduced largely in ICA69 knockout mice. The pain hypersensitivity was enhanced in the second phase 7 days after formalin administration. Meanwhile, increased Ser880 phosphorylation in GluA2 and decreased surface GluA2 were concordant with the pain. Furthermore, the number of activated microglia in spinal dorsal horn increased in line with pain hypersensitivity. Together, ICA69 deficiency promoted the internalization of GluA2 and FML-induced long-lasting pain hypersensitivity. In addition, microglia activation might be an important factor in the development of the pain hypersensitivity.
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.
authors.forename: Qian-Jun
authors.initials: QJ
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Yao
authors.forename: Shen-Hui
authors.initials: SH
authors.lastname: Jin
authors.forename: Mei-Zi
authors.initials: MZ
authors.lastname: Qian
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Li
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Zhang
authors.forename: Bin-Yu
authors.initials: BY
authors.lastname: Chen
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.forename: Jun-Lu
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D005557:Formaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D006614:Hindlimb / Q000187:drug effects* / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
chemical_list: D001324:Autoantigens; C490184:Ica1 protein, mouse; D005557:Formaldehyde