Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model

摘要

The aim of this study was to determine whether pregabalin affects nociceptive behavior and central sensitization in a trigeminal neuropathic pain model. A partial infraorbital nerve transection (p-IONX) or sham operation was performed in adult male rats. Nociceptive withdrawal thresholds were tested with von Frey filaments applied to the bilateral vibrissal pads pre-operatively and post-operatively. On post-operative day 7, the behavioral assessment was conducted before and at 30 min, 60 min, 120 min, 180 min, and 24hr after pregabalin (0.1, 1, 10, 100 mg/kg, i.p.) or saline injection. The effects of pregabalin or saline were also examined on the mechanoreceptive field and response properties of nociceptive neurons recorded in the medullary dorsal horn at post-operative day 7–10. Reduced withdrawal thresholds reflecting bilateral mechanical allodynia were observed in p-IONX rats until post-operative day 28, but not in sham-operated rats. At post-operative day 7, pregabalin significantly and dose-dependently reversed the reduced mechanical withdrawal thresholds in p-IONX rats. Pregabalin also attenuated central sensitization of the neurons, as reflected in reversal of their reduced activation threshold, increased responses to pinch/pressure, and enhanced stimulus-response function. This study provides the first documentation that pregabalin attenuates the mechanical allodynia and central sensitization that characterize this trigeminal neuropathic pain model, and supports its clinical use for treating craniofacial neuropathic pain.