抄録
Spinal mechanisms of hyperalgesia is believed to be caused by a series of actions, including activation of NMDA receptors with an increase in intracellular NO in the second-order neurons of the spinal cord dorsal horn, activation of guanyl cyclase (GC) and the subsequent activation of protein kinase, and gene expression. We investigated the influence of NO increase on NMDA receptors and the subsequent involvement of GC. Exposed rabbit spinal cords were irrigated with SNP, as an NO source, and WDR neuron activity was measured electrophysiologically by an extracellular microelectrode. Spontaneous and pinching-induced activities of the WDR neurons were also measured after irrigating with SNP only, a mixture of SNP and MK801 (NMDA recep tor antagonist), a mixture of SNP and MB (GC inhibitor), or a mixture of SNP and HB (NO scavenger).
In the SNP group the numbers of both spontaneous and pinching-induced activities increased, and the increase in neuronal activity after pinching lasted for approximately 2 hours. There were no significant differ ences in the number of either spontaneous or induced activities after administrating the mixture of SNP and MK801 compared to the SNP group.However, the duration of increased activity decreased significantly. In the SNP/MB and SNP/HB groups there was a significant reduction in both spontaneous and induced activities compared to the SNP group.
From the data above hyperalgesia caused by SNP could be related to NO. Because there was no significant difference in neuronal activity between the SNP group and the mixture of SNP and MK801 group, MK801 seemed not to inhibit hyperalgesia easily once it was induced in the spinal cord dorsal horn. GC activation and cGMP hyperfunction associated with increased NO were assumed to participate in hyperalgesia, as the mixture of SNP and MB did not make significant changes in both spontaneous and induced activities.Both spontaneous and induced activities were stayed in the control level after irrigation with SNP and HB, which confirmed that NO played a role in increasing WDR neuron activity.
NO delivered from SNP was speculated to continuously increase spontaneous WDR neuron activity, and to accentuate stimuli-induced activity, contributing to central sensitization in the spinal cord.
