PLACEBO ANALGESIA 1 Placebo Analgesia

SUMMARY The expectation of pain relief can exert a powerful analgesic effect, even when pain is severe. Depending on the nature of experiences and instructions provided, a placebo analgesic effect can be elicited acutely in a very large percentage of individuals, in both experimental and clinical contexts. Placebo analgesia has been linked with activity in the prefrontal cortex, endogenous opioid release in both descending antinociceptive systems and forebrain structures, and reduced responses to noxious stimulation in regions of anterior cingulate and insular cortex, thalamus, spinal cord that correlate with the reported relief of pain. Thus, placebo responses can affect pain via both inhibition of ascending nociceptive pathways and modulation of forebrain and limbic pain-generation circuits. However, placebo responses are heterogeneous, and the degree to which each mechanism is involved likely depends in part on (a) the combination of conditioning and expectation elicited by the treatment context, and (b) inter-individual differences in optimism, receptivity to the placebo, and brain opioid and dopamine systems, as well as other factors. A more complete understanding of the placebo analgesic response could lead to new treatments that exploit psychological methods for activating pain-modulating circuitry and for ethically and optimally enhancing the placebo component of active treatments.