Background and aims: Animals and humans are able to inhibit pain without pain-relieving medications by activating their own endogenous pain inhibition system. Placebo and conditioned pain modulation (CPM) are two prominent paradigms testing endogenous pain inhibition. Although the ability varies tremendously among individuals, several CPM studies have shown that endurance athletes possess a better endogenous pain inhibition system than healthy controls. 
Methods: Here we investigated 16 endurance athletes (mean training frequency 9.3 h/week) and 17 healthy non-athletes (mean training frequency 0 h/week) in well-established placebo and CPM paradigms to assess whether the mechanisms of CPM and placebo are the same. 
Results: We found a significantly greater CPM effect in athletes than in non-athletes. In contrast, we could only find a significant placebo effect in non-athletes. Interestingly, there was a negative association between CPM effect and placebo effect in non-athletes, but a positive trend in athletes. Furthermore, we found a strong positive association between CPM effect and exercise-induced hypoalgesia, and negative associations between placebo effect and heart rate variability, as well as between placebo effect and interoceptive awareness. 
Conclusions: Together, our results demonstrate a double dissociation of endogenous pain inhibition of CPM and placebo effect between endurance athletes and non-athletes, indicating that both effects do not rely on the same mechanism. Our results are compatible with the suggestion that CPM hypoalgesia involves other key structures in the brainstem and therewith other top-down pain inhibition pathways than placebo.

DOUBLE DISSOCIATION OF ENDOGENOUS PAIN INHIBITION DUE TO CONDITIONED PAIN MODULATION AND PLACEBO IN HUMANS