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EphrinB-EphB receptor tyrosine kinases have been demonstrated to play important roles in pain processing after peripheral nerve injury. We have previously reported that ephrinB-EphB receptor signaling can regulate excitability and plasticity of neurons in spinal dorsal horn, and thus contribute to spinal central sensitization in neuropathic pain. How EphB receptor activation influences excitability of primary neurons in dorsal root ganglion (DRG), however, remains unknown. Here we report that EphB receptor activation facilitates calcium influx through NMDA receptor dependent and independent manners. In cultured DRG cells from adult rats, EphB1 and EphB2 receptors were expressed in neurons, but not the glial cells. Bath application of EphB receptor agonist ephrinB2-Fc induced NMDA-independent Ca influx, which was from the extracellular space rather than endoplasmic reticulum. EphB receptor activation also greatly enhanced NMDA-dependent Ca influx and NR2B phosphorylation, which was prevented by pre-treatment of Src kinase inhibitor PP2. In nerve-injured DRG neurons, elevated expression and activation of EphB1 and EphB2 receptors contributed to the increased intracellular Ca concentration and NMDA-induced Ca influx. Repetitive intrathecal administration of EphB2-Fc inhibited the increased phosphorylation of NR2B and Ca-dependent subsequent signals Src, ERK, and CaMKII as well as behaviorally expressed pain after nerve injury. These findings demonstrate that activation of EphB receptors can modulate DRG neuron excitability by facilitating Ca influx directly or through Src kinase activation-mediated NMDA receptor phosphorylation and that EphB receptor activation is critical to DRG neuron hyperexcitability, which has been considered critical to the subsequent spinal central sensitization and neuropathic pain.
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Sensory neuronopathies affect sensory neuron in the posterior spinal ganglion. They are responsible for pain, balance disorder (ataxia) and the use of hands. They depend on multiple etiolo...
The purpose of this study is to determine whether patients with neuropathic pain has abnormal excitability in somatosensory cortex and abnormal sensory-motor connections.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
Loss of the ability to comprehend the meaning or recognize the importance of various forms of stimulation that cannot be attributed to impairment of a primary sensory modality. Tactile agnosia is characterized by an inability to perceive the shape and nature of an object by touch alone, despite unimpaired sensation to light touch, position, and other primary sensory modalities.
Cell adhesion molecules that mediate neuron-neuron adhesion and neuron-astrocyte adhesion. They are expressed on neurons and Schwann cells, but not astrocytes and are involved in neuronal migration, neurite fasciculation, and outgrowth. Ng-CAM is immunologically and structurally distinct from NCAM.
Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.
Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.
Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Some illnesses can be excruci...
Pain is a feeling (sharp or dull) triggered in the nervous system which can be transient or constant. Pain can be specific to one area of the body eg back, abdomen or chest or more general all over the body eg muscles ache from the flu. Without pain ...