Intracisternal antidepressants suppressed the nociceptive jaw opening reflex in freely moving rats

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 μsec duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of 15 μg imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to 76±6% of the control. Intracisternal administration of 30 μg desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to 48 ± 2, 27±8, or 25 ± 5 % of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from 23±2 to 69±4%, from 32±5 to 80±9%, and from 24±6 to 77±5% of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.