Abstract:
:Wnt5b, a member of Wnt family, plays multiple roles in tumor progression and metastasis. However, whether Wnt5b contributes to the sensitization of dorsal root ganglia (DRG) neurons and pathogenesis of bone cancer pain still remains unclear. Here, we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor-bearing mice. Application of Wnt5b evoked an increased discharge frequency in isolated DRG neurons and pain hypersensitivity in naïve mice which were almost completely prevented by anti-Ryk antibody. Moreover, intrathecal injection of anti-Ryk antibody to tumor-bearing mice significantly inhibited bone cancer-induced mechanic allodynia and thermal hyperalgesia. Subsequently, we also demonstrated that application of Wnt5b to cultured DRG neurons could enhance membrane P2X3 receptors and α,β-meATP-induced currents. Intrathecal injection of calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 or P2X3 receptors antagonist A317491 almost completely abolished Wnt5b-induced mechanical allodynia and thermal hyperalgesia in mice. Meanwhile, pretreatment with anti-Ryk antibody or CaMKII inhibitor KN93 can attenuate bone-cancer induced the upregulation of P2X3 membrane protein as well as pain hypersensitivity. These findings suggested that Wnt5b/Ryk promoted the trafficking of P2X3 receptors to the membrane via the activation of CaMKII in primary sensory neurons, resulting in peripheral sensitization and bone cancer-induced pain. Our results may offer a potential therapeutic strategy for bone cancer pain.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
He JJ,Wang X,Liang C,Yao X,Zhang ZS,Yang RH,Fang Ddoi
10.1016/j.expneurol.2020.113482subject
Has Abstractpub_date
2020-12-01 00:00:00pages
113482eissn
0014-4886issn
1090-2430pii
S0014-4886(20)30313-7journal_volume
334pub_type
杂志文章abstract::Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice u...
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