Background: It is now well established that wide dynamic range neurons (WDR) can possess widespread cutaneous inhibitory receptive fields, as well as excitatory receptive fields, in specific regions of the body. The ability of ketamine to depress the excitatory responses of spinal WDR neurons indicates that the analgesia produced by this agent may be a result, in part, of this spinal action. The primary purpose of this study was to investigate the effects of ketamine on the WDR propriospinal inhibitory mechanism that is induced by a bradykinin (BK) injection as a noxious test stimuli.
Methods: In decerebrate, spinal cord-transected cats (L1-L2), the effects of a low (0.5 mg.kg-1, intravenous) and a high (10 mg.kg-1, intravenous) dose of ketamine on the neuronal activity of spinal dorsal horn WDR neurons evoked by femoral artery injection of BK (10 micrograms) was examined. Extracellular activity was recorded from single WDR neurons that responded to noxious and innocuous stimuli applied to the cutaneous receptive fields on the foot pads of the left hind paw.
Results: After ipsilateral BK administration, the activity of the WDR neurons was found to be increased (excited) in all ten neurons that were examined. In contrast, the activity of these neurons was found to be decreased (inhibited) in five of these ten neurons after BK administration into the contralateral femoral artery. The 10 mg.kg-1 dose of ketamine significantly suppressed the excitatory activity observed in all 15 of the WDR neurons examined. A comparison of the effects produced by the 0.5-mg.kg-1 and the 10-mg.kg-1 intravenous doses reveals that the amount of suppression was dose-related. In addition, the inhibitory WDR neuronal activity induced by contralateral BK injection was also significantly reduced by both the 0.5- and the 10-mg.kg-1 doses of ketamine.
Conclusions: These results indicate that this reduction of excitatory and inhibitory responses of WDR neurons after noxious stimulation is likely to be the fundamental basis for the spinal cord component of ketamine-induced analgesia.