Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord.
In the present study we tested the effects of the antihyperalgesic compound gabapentin on dorsal horn neurones in adult spinal cord. Slices were taken from control and hyperalgesic animals suffering from streptozocin-induced diabetic neuropathy. At concentrations up to 100 microM, bath application failed to affect the resting membrane properties of dorsal horn neurones taken from both groups of animal. In contrast, bath application of gabapentin dramatically reduced the magnitude of the excitatory postsynaptic current (EPSC) in neurones taken from hyperalgesic animals without altering the magnitude of the EPSC in control animals. Using a paired pulse stimulation protocol, together with analysis of miniature EPSC's, it was possible to demonstrate that gabapentin mediated these effects via a pre-synaptic site of action.
Patel
M K
MK
Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge, CB2 2QB.
Gonzalez
M I
MI
Bramwell
S
S
Pinnock
R D
RD
Lee
K
K
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000150:complications; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D000077206:Gabapentin; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D013311:Streptozocin / Q000009:adverse effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D018692:Antimanic Agents; D003509:Cyclohexanecarboxylic Acids; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D013311:Streptozocin; D000077206:Gabapentin