Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial

Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM.

Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups.

Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p < 0.0001) but not in the placebo group (p = 0.56) (difference in correlation coefficients between groups; p = 0.004). Furthermore, the initial CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R²  = 0.51, p < 0.001, y = -0.54x + 2.98; placebo group: p = 0.56, significant difference in regression slopes; p = 0.015). These results indicate that pregabalin has a higher endogenous analgesic effect in individuals with lower original endogenous analgesia.

The analgesic effect of pregabalin depends on the original endogenous analgesia status. Its effect on conditioned pain modulation (CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia.