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

Soc Cogn Affect Neurosci. 2026 Mar 23:nsag018. doi: 10.1093/scan/nsag018. Online ahead of print.

ABSTRACT

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 firsthand 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, this double-blind placebo-controlled study (N = 35, 21 female) administered the opioid antagonist naltrexone and tested its effects on firsthand pain and affective and cognitive ratings of empathy for pain. While we predicted that naltrexone would increase both electrocutaneous and cold pain, as well as cognitive and affective aspects of empathy for pain, the results instead pointed in the other direction. While these hypo- rather than hyperalgesic effects were unexpected, the coherence in their directionality fits with previous findings and suggests the involvement of shared opioidergic mechanisms in the firsthand experience of pain and empathy for pain.

PMID:41872015 | DOI:10.1093/scan/nsag018