EphrinB–EphB signaling regulates spinal pain processing via PKCγ. (29th October 2015)

• Record Type: Journal Article
• Authors: Zhou, X.-L.; Zhang, C.-J.; Wang, Y.; Wang, M.; Sun, L.-H.; Yu, L.-N.; Cao, J.-L.; Yan, M.
• Is Part Of: Neuroscience. Volume 307(2015)
• Page Start: 64
• Page End: 72
• Publication Date: 2015-10-29
• Subjects: ANOVA analysis of variance -- CCI chronic constriction injury -- EDTA ethylenediaminetetraacetic acid -- EGTA ethylene glycol tetraacetic acid -- i.t. intrathecally -- NMDAR N-methyl-d-aspartate receptor -- PKCγ protein kinase C-γ -- PWL paw withdrawal latency -- PWT paw withdrawal threshold -- siRNA small interfering RNAs -- TCI tibia bone cavity tumor cell implantation; Eph -- ephrin -- protein kinase C -- central sensitization -- hyperalgesia; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.08.048
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: EphrinB2-Fc caused PKCγ activation. Knockdown of PKCγ prevented pain induced by ephrinB2-Fc. EphB2-Fc reduced PKCγ activation in pain models. 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.