Shared effects of the opioid antagonist naltrexone on first-hand and empathic pain

Empathy allows us to infer the affective state of another individual and resonate with it. Accumulating evidence suggests that on a neural level, empathizing relies on ‘shared neural representations’, i.e., patterns of neural activation recruited both during the first-hand and the empathic experience of a specific affective state. Studies employing placebo analgesia have shown consistent reductions in behavioral ratings and neural activity for both first-hand and empathic pain. The mechanistic interpretation of such effects, however, remains elusive, as placebo analgesia could exert its effects on empathy either via pharmacological actions or via top-down cognitive processes on pain and empathy beliefs. To address this limitation, we conducted a double-blind, within-subjects study administering either an opioid antagonist (naltrexone) or an inactive placebo in two separate testing sessions (N=35 healthy, neurotypical individuals, 21 female), and participants experienced both pain first-hand and pain empathy. We predicted that naltrexone would similarly increase first-hand pain and empathy for pain. The results, however, show reduced ratings of first-hand pain and empathy for pain, and thus, unexpectedly, hypo- rather than hyperalgesic effects. However, the coherence in their directionality confirms the hypothesis of shared opioidergic mechanisms being involved in the first-hand experience of pain and empathy for pain.