Circadian fluctuations in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat.

The 24-hour patterns of pain responsiveness and brain Met-enkephalin-like immunoreactivity (MLI) were determined in male Wistar rats housed under a 12-hour light and dark cycle (lights on from 0700 hr to 1900 hr). A circadian rhythm was observed in latencies to hot plate test (55 degrees C), showing the peak level near the onset of the dark phase (2000 hr). Pretreatment with naloxone (5 mg/kg, subcutaneously) decreased the highest latency (2000 hr), but did not change the lowest latency (1100 hr). In the mesolimbic area and the striatum, MLI had a negative correlation with the circadian fluctuation in pain sensitivity. MLI at 2000 hr was reduced significantly compared to that at 1100 hr in the basal ganglia, the frontal cortex and the substantia nigra. These results suggest that the circadian variation in hot plate latencies follows a circadian change in the activity of the endogenous opioid peptides system, and that Met-enkephalin may participate in the enhancement of the opioid system in the brain.