Fentanyl, an agonist at the mu opioid receptor, depresses pupillary unrest

- The magnitude of pupillary unrest in ambient light can be evaluated with the use of a portable infrared pupillometer.
- We theorized that inhibition of the Edinger-Westphal nucleus produces pupillary unrest and would be blocked by opioids.
- Fentanyl depressed pupillary unrest whereas light-induced miosis of the same degree had no effect.
- Pupillary unrest is depressed by the opioid fentanyl thus adding another objective measure of central opioid effect.

Pupillary unrest is a chaotic fluctuation in pupil size that is observed in darkness with the onset of drowsiness, and in ambient light. The mechanism of pupillary unrest in darkness as well as in ambient light is unknown but studies suggest that it is caused by fluctuating activity in the Edinger-Westphal (E.W.) nucleus. Neurons in the periaqueductal gray with oscillating firing patterns that are inhibitory to the E.W. nucleus have been described in the cat. We theorized that such oscillating neurons produce pupillary unrest in light and would be depressed by agents, such as opioids, known to depress inhibitory pathways in the midbrain. An infrared pupillometer was used to measure the effect of light on pupillary unrest in eight volunteer subjects, and on 20 patients scheduled for knee arthroscopy who received fentanyl as premedication. Pupillary unrest was quantified through spectral analysis of fast Fourier transforms. Sixteen-second measurements of pupil size at 33 Hz were filtered to eliminate blink artifacts and baseline drift. Pupillary unrest was augmented by excitation of the E.W. nucleus by light and was depressed by 40 ± 20% after the administration of the moderate dose of 1 mcg/kg of fentanyl. Recovery from the drug effect was observed. Based upon the data from this study we propose that pupillary unrest in light originates within oscillating inhibitory neurons that intermittently depress the E. W. nucleus.