Differential effects of persistent nociceptive stimulation on sleep stages

The purpose of this work was to investigate the sequence of modifications of sleep and pain parameters in a condition of persistent nociceptive stimulation. In freely moving cats carrying implanted electrodes, continuous polygraphic and behavioral recordings were collected 24 h a day for several consecutive days before and after treatment. Injection of formalin (2 ml, 37%) elicited continuous wakefulness (1-6 h) associated with behavioral manifestations of pain. This insomnia was followed by the delayed appearance of LS (light, slow wave sleep) DS (deep slow wave sleep) and REM (rapid eye movement sleep). On days 1 and 2 after injection, pain manifestations displayed a gradual decrease, while total sleep time (LS + DS + REM) slowly returned to normal levels. On day 1, the amount of LS was not modified, but DS and REM were greatly decreased. For 12 h after the first REM episode, REM was decreased while DS was already at the basal levels. Formalin elicited a long-lasting increase in EMG activity of the tibialis anterior muscle which was suppressed during REM and returned to higher levels afterwards. Prolonged wakefulness and delay in sleep stage appearance were also recorded when a 24-h sleep deprivation preceded formalin injection. In this condition, LS, DS and REM amount were at basal levels from their first reappearance, and a rebound in total sleep time and DS occurred on day 2 after the injection. After injection of smaller doses of formalin (0.5 ml, 8%), the amount of LS, DS and REM was at control levels since day 1. The results suggest that (1) the amount of sleep depends on sleep debt and on the level of pain intensity and (2) sleep stages are differentially sensitive to persistent pain.