title: Colocalization of insulin-like growth factor-1 receptor and T type Cav3.2 channel in dorsal root ganglia in chronic inflammatory pain mouse model.
abstract: Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays important roles in the nervous system. Increasing evidence supports that IGF-1 contributes to pain hypersensitivity through its insulin-like growth factor-1 receptor (IGF-1R) by activating IGF-1R/Akt or MAPK signaling pathways, whereas T-type Cav3.2 channel can facilitate and amplify pain signals originating from the sensory periphery. A recent study showed that activated IGF-1R can increase T-type Cav3.2 channel currents and further activate the G protein-dependent PKCα pathway to contribute to inflammatory pain sensitivity. However, the colocalization of IGF-1R and Cav3.2 in mouse dorsal root ganglion (DRG) under chronic inflammatory pain conditions remains elusive. In this study, we investigated changes in the expression of IGF-1R and the Cav3.2 channel, and their colocalization in mouse DRGs in chronic inflammatory pain condition (induced by complete Freund's adjuvant intraplanter injection) using real-time RT-PCR and immunohistochemistry approaches to confirm that Cav3.2 channel can mediate pain facilitation following IGF-1/IGF-1R signaling. We found that IGF-1R was expressed extensively in DRG neurons including small-, medium-, and large-sized neurons, whereas Cav3.2 channel was expressed exclusively in small-sized DRG neurons of naive mice. Expression of Cav3.2, but not IGF-1R, and colocalization of Cav3.2 and IGF-1R were increased in lumbar (L)4-L6 primary sensory neurons in DRGs of mice in chronic inflammatory pain. Moreover, the increased colocalization of IGF-1R and Cav3.2 is exclusively localized in small- and medium-sized primary sensory neurons. Our findings provided morphological evidence that T-type Cav3.2 channel, at least partially, mediates the pain facilitation of IGF-1/IGF-1R signaling in chronic inflammatory pain condition.
authors.affiliation: aDepartment of Anesthesiology, China-Japan Friendship Hospital, Beijing bJiangsu Province Key Laboratory of Anesthesiology, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu cInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science & Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Si-Fang
authors.initials: SF
authors.lastname: Lin
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Yu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Sun
authors.forename: Xing-Jun
authors.initials: XJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type; D007334:Insulin-Like Growth Factor I; D005620:Freund's Adjuvant