Inhibition of Protein Tyrosine Kinases Attenuated Aβ-Fiber-Evoked Synaptic Transmission in Spinal Dorsal Horn of Rats With Sciatic Nerve Transection

[摘要] References(45)Cited-By(2)Peripheral nerve injury leads to the establishment of a novel synaptic connection between afferent Aβ-fiber and lamina II neurons in spinal dorsal horn, which is hypothesized to underlie mechanical allodynia. However, how the novel synapses transmit nociceptive information is poorly understood. In the present study, the role of protein tyrosine kinases (PTKs) in Aβ-fiber-evoked excitatory postsynaptic currents (EPSCs) recorded in lamina II neurons in transverse spinal cord slices of rats was investigated using the whole-cell patch-clamp recording technique. In the slices from sciatic nerve transection (SNT) rats, genistein (50 μM), a broad-spectrum PTKs inhibitor, or PP2 (20 μM), a selective Src family tyrosine kinase inhibitor, significantly reduced the amplitude of Aβ-fiber EPSCs. In sham-operated rats, however, Aβ-fiber EPSCs were insensitive to genistein and PP2. The N-methyl-D-aspartate (NMDA) receptor antagonist AP-V (50 μM) suppressed Aβ-fiber EPSCs in slices from SNT rats but not from sham-operated rats. Following nerve injury, the slow inward currents elicited by bath application of NMDA (100 μM) significantly increased at −70 mV. In SNT rats, genistein and PP2 reduced Aβ-fiber-evoked EPSCs mediated by NMDA receptor; however, genistein produced little effect on Aβ-fiber EPSCs mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These data suggested that PTKs, especially Src family members, participated in Aβ-fiber-evoked synaptic transmission following sciatic nerve injury via potentiation of NMDA receptor function.

[学科分类] 药学

[关键词] neuropathic pain;allodynia;protein tyrosine kinase;Aβ-fiber;spinal dorsal horn