Phosphatidylinositol 3-kinase mediates pain behaviors induced by activation of peripheral ephrinBs/EphBs signaling in mice.
EphBs receptors and their ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Our recent evidence has shown that ephrinBs acted as a sensitizer to participate in peripheral sensitization and hyperalgesia induced by activation of peripheral ephrinBs/EphBs signaling. In the present study, we explored the role of phosphatidylinositol 3-kinase (PI3K) in ephrinB1-Fc-induced pain behaviors. Intraplantar injection of ephrinB1-Fc produced a time- and dose-dependent increase of PI3K-p110gamma expression and of phosphorylation of AKT in skin of injection site. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of peripheral AKT by ephrinB1-Fc. The activated AKT expressed in peripheral nerve terminals and DRG peptide-containing and small non-peptide-containing neurons. Inhibition of peripheral PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal Fos protein expression induced by intraplantar injection of ephrinB1-Fc. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in a dose-dependent manner. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling mediated pain behaviors induced by activation of peripheral ephrinBs/EphBs signaling in mice.
Guan
Xue-Hai
XH
Jiangsu Institute of Anesthesiology, Jiangsu Key Laboratory of Anesthesiology, 99 Huaihai West Road, Xuzhou 221002, PR China.
Lu
Xian-Fu
XF
Zhang
Hong-Xing
HX
Wu
Jing-Ru
JR
Yuan
Yan
Y
Bao
Qi
Q
Ling
Di-Yang
DY
Cao
Jun-Li
JL
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D036342:Ephrins / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D010146:Pain / Q000378:metabolism* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D036081:Receptors, Eph Family / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D036342:Ephrins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D036081:Receptors, Eph Family; D000077191:Wortmannin