The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia

<p>Abstract</p> <p>Background</p> <p>Gabapentin 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.</p> <p>Methods</p> <p>We 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).</p> <p>Results</p> <p>The 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.</p> <p>Conclusion</p> <p>We 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.</p

The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia-2

<p><b>Copyright information:</b></p><p>Taken from "The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia"</p><p>Journal of Neuroinflammation 2007;4():15-15.</p><p>Published online 5 Jun 2007</p><p>PMCID:PMC1892010.</p><p></p>ative doses of gabapentin in normal (A), arthritic (B) and neuropathic animals (C). The units were activated in three minute cycles by 10 s of noxious mechanical stimulation and 16 electrical pulses (2 ms pulse width, 1 Hz and twice the threshold intensity for the recruitment of C-fibers). Gabapentin was administered iv. in log2 cumulative doses every three cycles of stimulation (9 minutes) from 40 to 1,280 μmol/kg (7 to 224 mg/kg). The administration of gabapentin dose-dependently reduced the nociceptive responses in arthritic and neuropathic animals but not in normal rats

The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia-0

<p><b>Copyright information:</b></p><p>Taken from "The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia"</p><p>Journal of Neuroinflammation 2007;4():15-15.</p><p>Published online 5 Jun 2007</p><p>PMCID:PMC1892010.</p><p></p>rain of 16 electrical stimuli (B; wind-up). Top panel shows the number of spikes/s (sp/s) recorded for each stimulus as bar histograms (mechanical stimulation in mN and electrical pulses as TTL pulses)

The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia-1

<p><b>Copyright information:</b></p><p>Taken from "The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia"</p><p>Journal of Neuroinflammation 2007;4():15-15.</p><p>Published online 5 Jun 2007</p><p>PMCID:PMC1892010.</p><p></p>rence of the knee increased significantly 16 h after the injection of carrageenan. Neuropathy was induced seven days before the experiment following the partial sciatic nerve ligation technique. (B) Mechanical hyperalgesia was studied by applying a series of von Frey filaments previous to and at days 1, 4 (not shown) and 7 after the nerve ligation. (C) Thermal hyperalgesia was assessed by measuring paw withdrawal latencies to 55°C radiant heat using a similar timing. An intense mechanical and thermal hyperalgesia was observed in all tests made after the induction of neuropathy (**P < 0.01, ***P < 0.001, comparison vs. control response with the two tail unpaired t-test)