The Influence of placebo analgesia manipulations on pain report, the nociceptive flexion reflex, and autonomic responses to pain

Abstract

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.