Dose-response Suppression of Noxiously Evoked Activity of WDR Neurons by Spinally Administered Fentanyl

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Abstract
The influence of spinally administered fentanyl on the spontaneous and noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of decerebrate, spinal cord-transected cats was examined. This work was performed in order to evaluate the dose-response relationship, time course and naloxone reversibility of fentanyl suppression of neurons that are involved with the transmission of information about pain. Extracellular single neuron recordings were obtained from 18 WDR neurons in the lumbar enlargement. These neurons were activated by a radiant heat stimulus on the footpads of the hindpaw. Fentanyl (10, 15, 25 .mu.g in 0.5 ml of physiologic saline) was placed on the spinal cord following control studies of each neuron and the effect was observed. In 12 cats, 31 min after fentanyl administration, naloxone (0.1 mg) was administered i.v., and its effect on the fentanyl suppression was determined. All 3 doses of fentanyl suppressed both the spontaneous and evoked activity of all the neurons studied. Thirty min after fentanyl, the mean evoked activity was reduced to 47, 23 and 11% of control values by 10, 15 and 25 .mu.g, respectively. The spontaneous activity was reduced to similar levels. Naloxone (0.1 mg i.v.) caused a significant reversal of the fentanyl suppression. Fentanyl evidently causes a naloxone-reversible, dose-dependent suppression of noxiously evoked WDR neuron activity. Fentanyl is apparently acting through a specific drug-receptor interaction. The onset of neuronal suppression occurred more rapidly, and the duration of the suppression was longer following fentanyl than that seen following spinal morphine. The onset and duration of this suppression correlates well with human clinical data, providing further evidence that alterations of WDR neuronal activity may be important in the production of spinal opioid analgesia.

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