title: EphrinB-EphB signaling regulates spinal pain processing via PKCγ.
abstract: Spinal ephrinB-EphB signaling is involved in the modulation of pain processing. The aim of the present study was to investigate whether protein kinase C-γ (PKCγ) acts as a downstream effector in regulating spinal pain processing associated with ephrinB-EphB signaling in mice. The intrathecal injection of ephrinB2-Fc, an EphB receptor activator, caused thermal hyperalgesia and mechanical allodynia, as well as increased activation of spinal PKCγ. Knockdown of spinal PKCγ prevented the pain behaviors induced by ephrinB2-Fc. Furthermore, the intrathecal injection of EphB2-Fc, an EphB receptor blocker, suppressed formalin-induced inflammatory, chronic constriction injury (CCI)-induced neuropathic, and tibia bone cavity tumor cell implantation (TCI)-induced bone cancer pain behaviors, in addition to reducing the activation of spinal PKCγ. Finally, the intrathecal injection of MK801, an N-methyl-D-aspartate (NMDA) receptor blocker, prevented the pain behaviors and spinal PKCγ activation induced by ephrinB2-Fc. Overall, the results confirm the important role of PKCγ in the regulation of spinal pain processing associated with ephrinB-EphB signaling.
authors: Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors: X-L
authors: XL
authors: Zhou
authors: Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors: C-J
authors: CJ
authors: Zhang
authors: Department of Anesthesiology, Tai Zhou People's Hospital, Tai Zhou 225300, China.
authors: Y
authors: Y
authors: Wang
authors: Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221000, China.
authors: M
authors: M
authors: Wang
authors: Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221000, China.
authors: L-H
authors: LH
authors: Sun
authors: Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors: L-N
authors: LN
authors: Yu
authors: Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221000, China.
authors: J-L
authors: JL
authors: Cao
authors: Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China. Electronic address: zryanmin@zju.edu.cn.
authors: M
authors: M
authors: Yan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications; D004195:Disease Models, Animal; D036388:Ephrin-B2 / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005557:Formaldehyde / Q000633:toxicity; D006930:Hyperalgesia / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D036081:Receptors, Eph Family / Q000378:metabolism* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D036388:Ephrin-B2; D034741:RNA, Small Interfering; D005557:Formaldehyde; C087857:protein kinase C gamma; D036081:Receptors, Eph Family; D011493:Protein Kinase C
keywords: Eph; central sensitization; ephrin; hyperalgesia; protein kinase C