The Involvement of NMDA receptor in the intrinsic analgesia evoked by hyperventilation

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[background] Hyperventilation may increase the excitatory amino acid concentration in the CNS. But, there was no report about such effects of hyperventilation. We have investigated the role of NMDA receptors in the rat dorsal horn in mediating neuronal responses when hyperventilation was administered. [method] Male Spargue-Dawley rats were anesthetized with halothane. Following tracheotomy, the animals were mechanically ventilated. Catheters were inserted into veins and arteries and laminectomy was made and the spinal cord was transected. Animals were fixed on a stereotaxic frame. Following surgery, a light level of anesthesia was maintained. Extra-cellular single-cell action potentials were recorded and spike firing rate were measured. The WDR cell was identified by the modality and by the depth from the cord dorsum. Four groups were studied : 1. The competitive NMDA receptor antagonist, 2-Amino-5-phosphonovaleric, AP5 0.16 μmol was applied onto the spinal cord, both the spontaneous a … More nd evoked firing rate were recorded. 2. Hyperventilation group. Hyperventilation was administered and 60 minutes later, returned to normal ventilation. 3. Pre-treatment study. AP5 was applied onto the spinal cord. The responses to AP5 administration were recorded. Subsequently, the effect of respiratory hyperventilation was studied by increasing the respiratory frequency and tidal volume. The firing rates were recorded. 4. Post-treatment study. Hyperventilation was administered, and fifty minutes later, AP5 was administered, and the time course of AP5 was studied. [Results] AP5 at low dose had no effect on the single-unit activity of WDR cell. Hyperventilation depressed dorsal horn neuronal activity. After hyperventilation, the administration of AP5 at low dose profoundly enhanced the depressing effect of hyperventilation. [Conclusion] Our results suggest that hyperventilation activates NMDA receptors, thereby attenuating the inhibitory effect of hyperventilation on the neuronal activity. Less