Microinjection of glutamate into the amygdala modulates nociceptive and cardiovascular response in freely moving rats

This study was performed to examine the mean arterial pressure and nociceptive jaw opening reflex after microinjection of glutamate into the amygdala in freely moving rats, and to investigate the mechanisms of antinociceptive action of amygdala. Animals were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula (26 gauge) was implanted in the amygdala and lateral ventricle. Stimulating and recording electrodes were implanted into each of 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. After 48 hours of recovery from surgery, mean arterial pressure and digastric electromyogram (dEMG) were monitored in freely moving rats. Electrical shocks (200 musec duration, 0.5~2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minutes. After injection of 0.35 M glutamate into the amygdala, mean arterial pressure was increased by 8+/-2 mmHg and dEMG was suppressed to 71+/-5% of the control. Injection of 0.7 M glutamate elevated mean arterial pressure by 25+/-5 mmHg and suppressed dEMG to 20+/-7% of the control. The suppression of dEMG were maintained for 30 minutes. Naloxone, an opioid receptor antagonist, inhibited the suppression of dEMG elicited by amygdaloid injection of glutamate from 28+/-4 to 68+/-5% of the control. Methysergide, a serotonin receptor antagonist, also inhibited the suppression of dEMG from 33+/-5 to 79+/-4% of the control. However, phentolamine, an alpha-adrenergic receptor antagonist, did not affect the suppression of dEMG. These results suggest that the amygdala can modulate both cardiovascular and nociceptive responses and that the antinociception of amygdala seems to be attributed to an augmentation of descending inhibitory influences on nociceptive pathways via serotonergic and opioid pathways.

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 musec duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of 15 microgram imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to 76+/-6% of the control. Intracisternal administration of 30 jig 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.