Antinociceptive effects of mirtazapine, pregabalin, and gabapentin after chronic constriction injury of the infraorbital nerve in rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Intraspinal administration of either mirtazapine, gabapentin, or pregabalin reverses the lowered facial mechanical thresholds produced in a rat model of trigeminal neuropathic pain.
Kunihiro
K
Nakai
Aya
A
Nakae
Ryota
R
Hashimoto
Takashi
T
Mashimo
Ko
K
Hosokawa
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000588:Amines / Q000008:administration & dosage / Q000627:therapeutic use*; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D020209:Cranial Nerve Injuries / Q000150:complications; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000188:drug therapy*; D000077206:Gabapentin; D007278:Injections, Spinal; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D009437:Neuralgia / Q000188:drug therapy*; D059226:Nociceptive Pain / Q000188:drug therapy; D009915:Orbit / Q000294:innervation; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014110:Touch / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D008803:Mianserin; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000078785:Mirtazapine