The Influence of Placebo Analgesia Manipulations on Pain Report, the Nociceptive Flexion Reflex, and Autonomic Responses to Pain.

Expectations for pain relief and experience/conditioning are psychological factors that contribute to placebo analgesia, yet few studies have studied the physiological mechanisms underlying their effects. This study randomized 133 participants to 4 groups: an expectation only (E-only) group, a conditioning only (C-only) group, an expectation plus conditioning (E+C) group, and a natural history (NH) control group. Painful electric stimulations were delivered before and after an inert cream was applied to the site of stimulation. Pain-related outcomes (pain ratings, nociceptive flexion reflex [NFR], skin conductance response, and heart rate acceleration) were recorded after each stimulation. NFR (a measure of spinal nociception) assessed if placebo analgesia inhibited spinal processing of pain. E+C was the only manipulation that significantly inhibited pain and skin conductance response. Surprisingly, NFR was facilitated in the E+C and E-only groups. No effects were noted for C-only. Mediation analysis suggested 2 descending processes were engaged during E+C that influenced spinal nociception: 1) descending facilitation and 2) descending inhibition that was also responsible for pain reduction. These results suggest that E+C manipulations produce the strongest analgesia and have a complex influence on spinal nociception involving both inhibitory and facilitatory processes. PERSPECTIVE: This study assessed whether placebo analgesia manipulations that include expectations, conditioning, or both modulate the NFR (measure of spinal nociception). Only the manipulation that involved expectations and conditioning inhibited pain, but both expectation manipulations facilitated NFR. This suggests a complex modulation of spinal neurons by placebo manipulations.