Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats.
BACKGROUND
Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury.


METHODS
Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 microM).


RESULTS
Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolarization, and shortened the after hyperpolarization following an AP. In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization.


CONCLUSIONS
Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function.
Kanai
A
A
Department of Anesthesiology, Kitasato University of Medicine, Sagamihara, Japan. kanaiakifumi@aol.com
Sarantopoulos
C
C
McCallum
J B
JB
Hogan
Q
Q
D000085:Acetates / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000588:Amines; D000700:Analgesics / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004594:Electrophysiology; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D012584:Sciatic Nerve / Q000293:injuries*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin