Inflammation unmasks gabapentin's effect on A delta-fiber evoked excitatory postsynaptic currents in substantia gelatinosa neurons of rat spinal cord.
OBJECTIVE
To study the analgesic mechanism of gabapentin, an anticonvulsant, during antinociceptive clinical treatment.


METHODS
Whole-cell voltage-clamp recordings were taken from adult rat spinal cord slices to investigate the effect of gabapentin on primary afferent A delta-fiber evoked excitatory postsynaptic currents (EPSCs) to substantia gelatinosa (SG) neurons in normal and inflamed (established by plantar injection of carrageenan) rats.


RESULTS
Gabapentin (5 - 20 micro mol/L for 5 min) depressed dorsal root A delta fiber evoked polysynaptic, but not monosynaptic EPSCs to SG experiencing inflammation by about 25% (n = 10, P < 0.01). However, gabapentin did not depress the evoked polysynaptic or monosynaptic EPSCs in normal rats. Gabapentin failed to block a glutamate receptor subtype, N-methyl-D-aspartate (NMDA), -induced slow excitatory currents on SG neurons.


CONCLUSIONS
Inflammation, at least in part, unmasks the gabapentin depression on nociception transmission in the dorsal horn, and this depression is not due to the blockade of postsynaptic NMDA receptor.
Liu
Zhiliang
Z
Department of Neurosurgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. zl-liu@163.net
Xu
Ruxiang
R
Yang
Kun
K
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin