title: Involvement of CX3CR1 in bone cancer pain through the activation of microglia p38 MAPK pathway in the spinal cord.
abstract: Previous studies have demonstrated that fractalkine, a newly discovered chemokine, is implicated in spinal cord neuron-to-microglia activation signaling as well as mediation of neuropathic and inflammatory pain via its sole receptor CX3CR1, which is specifically expressed on microglia. However, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms have not been elucidated. In this study we utilized a Sprague-Dawley rat animal model, and our findings indicated that on day 6, 12, and 18 following bone cancer pain induced by Walker 256 cell inoculation, the expression level of CX3CR1 in the spinal cord gradually increased. Intrathecal injection of a neutralizing antibody against CX3CR1 not only delayed the initiation of mechanical allodynia, but also attenuated established pain sensitization of BCP rats. Furthermore, we demonstrated that blockade of CX3CR1 suppressed the activation of microglia and the expression of p38 mitogen-activated protein kinase (MAPK) in the spinal cord in BCP rats. These results suggest a new mechanism of BCP, in which the microglia CX3CR1/p38 signaling cascade potentially plays an important role in facilitating pain processing in BCP rats.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. szhujh@gmail.com
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Hu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Cai-Fang
authors.initials: CF
authors.lastname: Li
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.forename: Fu-Hai
authors.initials: FH
authors.lastname: Ji
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D059350:Chronic Pain / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017628:Microglia / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D019707:Receptors, Chemokine; D048051:p38 Mitogen-Activated Protein Kinases