The transmission of endogenous opioids may be responsible for placebo analgesia by fostering pain suppression. Using molecular imaging techniques, Zubieta et al. examined the activity of the endogenous opioid system in patients with chronic pain. They found that placebo agents could activate regional opioid neurotransmission, and this activation correlated with lower pain ratings (Zubieta et al. 2005). To further test this mechanism, Levine et al. examined whether an opioid antagonist, naloxone, could block placebo-induced pain relief. They found that among the subset of patients whose pain improved with placebo administration, the added administration of naloxone inhibited the pain relief (Levine et al. 1978). This suggests that placebo-induced analgesia was mediated by the release of endogenous opioids.
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