pregabalin and Cranial-Nerve-Injuries

To clarify the antiallodynic effects of the α2-adrenergic receptor antagonist mirtazapine compared with those of gabapentin and pregabalin in a rat model of orofacial neuropathic pain.. Mirtazapine (10, 30, and 100 μg), gabapentin (10, 30, and 100 μg), and pregabalin (3, 10, and 30 μg) were administered intrathecally to eight male Sprague-Dawley rats with orofacial neuropathic pain induced by chronic constriction injury of the infraorbital nerve that had been carried out 2 weeks previously. Stimulation using von Frey filaments (1.0 to 15.0 g) applied to skin innervated by the injured infraorbital nerve enabled the measurement of mechanical thresholds 0 to 180 minutes after drug injection. Time-course data for the dose-response effects were analyzed using two-way analysis of variance and the posthoc Tukey-Kramer multiple-comparison test.. Intrathecal administration of not only gabapentin and pregabalin but also mirtazapine reversed the lowered mechanical nociceptive thresholds produced by the nerve injury. The ED50 (95% confidence interval) was (in μg) 49.00 (39.71-58.29) for mirtazapine, 54.84 (46.12-63.56) for gabapentin, and 13.47 (11.24-15.69) for pregabalin.. Intraspinal administration of either mirtazapine, gabapentin, or pregabalin reverses the lowered facial mechanical thresholds produced in a rat model of trigeminal neuropathic pain.

Topics: Adrenergic alpha-Antagonists; Amines; Analgesics; Animals; Cranial Nerve Injuries; Cyclohexanecarboxylic Acids; Disease Models, Animal; Dose-Response Relationship, Drug; Facial Pain; Gabapentin; gamma-Aminobutyric Acid; Injections, Spinal; Male; Mianserin; Mirtazapine; Neuralgia; Nociceptive Pain; Orbit; Pain Threshold; Pregabalin; Rats; Rats, Sprague-Dawley; Time Factors; Touch

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- and postoperatively. On postoperative day 7, the behavioral assessment was conducted before and at 30, 60, 120, and 180 minutes after and 24 hours after pregabalin (.1, 1, 10, 100 mg/kg intraperitoneally) 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 postoperative days 7 to 10. Reduced withdrawal thresholds reflecting bilateral mechanical allodynia were observed in p-IONX rats until postoperative day 28, but not in sham-operated rats. At postoperative 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.. Trigeminal nerve injury in rats produced facial mechanical hypersensitivity and trigeminal central sensitization of medullary dorsal horn neurons that were markedly attenuated by systemically administered pregabalin, suggesting its potential clinical utility for orofacial neuropathic pain.

Topics: Analgesics; Animals; Behavior, Animal; Cranial Nerve Injuries; Electric Stimulation; Facial Pain; gamma-Aminobutyric Acid; Hot Temperature; Male; Nociception; Nociceptors; Pain Threshold; Physical Stimulation; Posterior Horn Cells; Pregabalin; Rats; Rats, Sprague-Dawley; Trigeminal Neuralgia; Vibrissae