Dual effect of dynorphin A on single-unit spike potentials in rat trigeminal nucleus

The amygdala is known as a site for inducing analgesia, but its action on the trigeminal nucleus has not been known well. Little information is available on the effect of dynorphin on NMDA receptor-mediated electrophysiological events in the trigeminal nucleus. The purpose of this study was to investigate the changes in the single neuron spikes at the trigeminal nucleus caused by the amygdala and the action of dynorphin on the trigeminal nucleus. In the present study, extracellular single unit recordings were made in the dorsal horn of the medulla (trigeminal nucleus caudalis) and the effects of microiontophoretically applied compounds were examined. When (D-Ala2, N-Me-Phe4, Glys5-ol)enkephalin (DAMGO, 10-25 mM), a mu-opioid receptor agonist, was infused into the amygdala, the number of NMDA-evoked spikes at the trigeminal nucleus decreased. However, the application of naloxone into the trigeminal nucleus while DAMGO being infused into the amygdala increased the number of spikes. Low dose (1 mM) of dynorphin in the trigeminal nucleus produced a significant decrease in NMDA-evoked spikes of the trigeminal nucleus but the NMDA-evoked responses were facilitated by a high dose (5 mM) of dynorphin. After the kappa receptors were blocked with naloxone, dynorphin induced hyperalgesia. After the NMDA receptors were blocked with AP5, dynorphin induced analgesia. In conclusion, dynorphin A exerted dose-dependent dual effects (increased & decreased spike activity) on NMDA-evoked spikes in the trigeminal nucleus. The inhibitory effect of the dynorphin at a low concentration was due to the activation of kappa receptors and the excitatory effect at a high concentration was due to activation of NMDA receptors in the trigeminal neurons.

Hemorrhage- and restraint-induced analgesia in male and female conscious rats

It is well known that stress induces analgesia. This study was designed to demonstrate the stress-induced analgesia by employing hemorrhage and restraint and to investigate its mechanism and sex difference. The degree of pain was assessed by measuring the magnitude of jaw opening reflex produced by a noxious electrical stimulation in the dental pulp and by measuring the latency to withdraw the tail from a heat ray. Restraint showed an antinociceptive response. A significant increase in pain threshold on bleeding was shown and the increase was larger in male group than in female group. The tail flick latency (TFL) on bleeding after AVP antagonist injection into the ventricle was decreased and the decrease was greater in male rats than in female rats. Castration resulted in a significant reduction of TFL. This effect was reversed by treatment with sex hormones. TFL was decreased during hemorrhage in castrated rats. This response was opposite to that in non-castrated rats. TFL was further decreased during hemorrhage after infusion of AVP antagonist, and there was a significant sex difference. These results suggest that both restraint and hemorrhage produce an antinociception and that, in hemorrhage-induced analgesia, AVP and sex hormones may play an important role and male rats show a greater analgesic response.