Inhibition of protein tyrosine kinases attenuated abeta-fiber-evoked synaptic transmission in spinal dorsal horn of rats with sciatic nerve transection.
Peripheral nerve injury leads to the establishment of a novel synaptic connection between afferent Abeta-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 Abeta-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 microM), a broad-spectrum PTKs inhibitor, or PP2 (20 microM), a selective Src family tyrosine kinase inhibitor, significantly reduced the amplitude of Abeta-fiber EPSCs. In sham-operated rats, however, Abeta-fiber EPSCs were insensitive to genistein and PP2. The N-methyl-D-aspartate (NMDA) receptor antagonist AP-V (50 microM) suppressed Abeta-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 muM) significantly increased at -70 mV. In SNT rats, genistein and PP2 reduced Abeta-fiber-evoked EPSCs mediated by NMDA receptor; however, genistein produced little effect on Abeta-fiber EPSCs mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These data suggested that PTKs, especially Src family members, participated in Abeta-fiber-evoked synaptic transmission following sciatic nerve injury via potentiation of NMDA receptor function.
Hu
Xiao-Dong
XD
Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, China.
Hu
Neng-Wei
NW
Xin
Wen-Jun
WJ
Zhou
Li-Jun
LJ
Zhang
Tong
T
Liu
Xian-Guo
XG
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology
D004791:Enzyme Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases