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Antinociceptive Effects of Mirtazapine, Pregabalin, and Gabapentin After Chronic Constriction Injury of the Infraorbital Nerve in Rats

  • Kunihiro Nakai1,2
  • Aya Nakae3,*,
  • Ryota Hashimoto4,5
  • Takashi Mashimo3
  • Ko Hosokawa2

1Department of Plastic & Reconstructive Surgery, Osaka University, Graduate School of Medicine, Osaka, Japan

2Department of Plastic Surgery, Osaka University, Graduate School of Medicine, Osaka, Japan

3Department of Anesthesiology & Intensive Care, Osaka University, Graduate School of Medicine, Osaka, Japan

4Molecular Research Center for Children’s Mental Development, United Graduate School of Child, Osaka University, Osaka, Japan

5Department of Psychiatry, Graduate School of Medicine, Osaka University, Osaka, Japan

DOI: 10.11607/jop.1105 Vol.28,Issue 1,March 2014 pp.61-67

Published: 30 March 2014

*Corresponding Author(s): Aya Nakae E-mail:


Aims: 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 post-hoc 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. Conclusion: Intraspinal administration of either mirtazapine, gabapentin, or pregabalin reverses the lowered facial mechanical thresholds produced in a rat model of trigeminal neuropathic pain.


allodynia; gabapentin; mirtazapine; orofacial pain; pregabalin

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Kunihiro Nakai,Aya Nakae,Ryota Hashimoto,Takashi Mashimo,Ko Hosokawa. Antinociceptive Effects of Mirtazapine, Pregabalin, and Gabapentin After Chronic Constriction Injury of the Infraorbital Nerve in Rats. Journal of Oral & Facial Pain and Headache. 2014. 28(1);61-67.


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