Abstract
BackgroundGabapentin is a structural analogue of gamma-aminobutyric acid with strong anticonvulsant and analgesic activities. Important discrepancies are observed on the effectiveness and potency of gabapentin in acute nociception and sensitization due to inflammation and neuropathy. There is also some controversy in the literature on whether gabapentin is only active in central areas of the nervous system or is also effective in the periphery. This is probably due to the use of different experimental models, routes of administration and types of sensitization. The aim of the present study was to investigate the influence of the spinal cord sensitization on the antinociceptive activity of gabapentin in the absence and in the presence of monoarthritis and neuropathy, using the same experimental protocol of stimulation and the same technique of evaluation of antinociception.MethodsWe studied the antinociceptive effects of iv. gabapentin in spinal cord neuronal responses from adult male Wistar rats using the recording of single motor units technique. Gabapentin was studied in the absence and in the presence of sensitization due to arthritis and neuropathy, combining noxious mechanical and repetitive electrical stimulation (wind-up).ResultsThe experiments showed that gabapentin was effective in arthritic (max. effect of 41 ± 15% of control and ID50 of 1,145 ± 14 micromol/kg; 200 mg/kg) and neuropathic rats (max. effect of 20 ± 8% of control and ID50 of 414 ± 27 micromol/kg; 73 mg/kg) but not in normal rats. The phenomenon of wind-up was dose-dependently reduced by gabapentin in neuropathy but not in normal and arthritic rats.ConclusionWe conclude that systemic gabapentin is a potent and effective antinociceptive agent in sensitization caused by arthritis and neuropathy but not in the absence of sensitization. The potency of the antinociception was directly related to the intensity of sensitization in the present experimental conditions. The effect is mainly located in central areas in neuropathy since wind-up was significantly reduced, however, an action on inflammation-induced sensitized nociceptors is also likely.
Highlights
Gabapentin is a structural analogue of gamma-aminobutyric acid with a strong anticonvulsant activity
The mean forces used for mechanical stimulation in the three experimental groups were 0.8 ± 0.1 N in normal animals, 0.8 ± 0.1 N in arthritic animals, and 0.9 ± 0.1 N in animals with neuropathy
Mean control number of responses elicited by noxious mechanical stimulation was very similar in the three groups: 372 ± 47 spikes in normal animals, 298 ± 24 spikes in arthritis and 315 ± 19 spikes in neuropathy
Summary
Gabapentin is a structural analogue of gamma-aminobutyric acid with strong anticonvulsant and analgesic activities. There is some controversy in the literature on whether gabapentin is only active in central areas of the nervous system or is effective in the periphery This is probably due to the use of different experimental models, routes of administration and types of sensitization. Gabapentin is a structural analogue of gamma-aminobutyric acid with a strong anticonvulsant activity It is an effective agent in the treatment of neuropathic pain [1,2] with a mechanism of action, that was initially thought to involve the modulation of GABA-ergic transmission, but that it currently seems more related to the blockade of voltage-gated calcium channels [3,4,5,6]. Opposite results have been reported when studying the antinociceptive activity of gabapentin in the absence of sensitization, ranging from a facilitation of nociceptive neuronal activity [12] to a virtual full inhibition of responses [20]
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