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Inhibition of protein tyrosine kinases attenuated abeta-fiber-evoked synaptic transmission in spinal dorsal horn of rats with sciatic nerve transection.
- Source :
-
Journal of pharmacological sciences [J Pharmacol Sci] 2006 Sep; Vol. 102 (1), pp. 64-71. Date of Electronic Publication: 2006 Aug 26. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Animals
Electric Stimulation
Electrophysiology
Enzyme Inhibitors pharmacology
Excitatory Postsynaptic Potentials drug effects
In Vitro Techniques
Male
Patch-Clamp Techniques
Protein-Tyrosine Kinases metabolism
Rats
Rats, Sprague-Dawley
Receptors, AMPA antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Sciatic Nerve injuries
Spinal Cord cytology
Spinal Cord physiology
src-Family Kinases physiology
Nerve Fibers, Myelinated physiology
Posterior Horn Cells physiology
Protein-Tyrosine Kinases antagonists & inhibitors
Sciatic Nerve physiology
Synaptic Transmission physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1347-8613
- Volume :
- 102
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 16936453
- Full Text :
- https://doi.org/10.1254/jphs.fp0060492