Neuroscientific evidence for pain being a classically conditioned response to trauma- and pain-related cues in humans

Psychological trauma is typically accompanied by physical pain, and posttraumatic stress disorder (PTSD) often co-occurs with chronic pain. Clinical reports suggest that pain after trauma may be part of a re-experiencing symptomatology. Classical conditioning can underlie visual re-experiencing since intrusions can occur as conditioned responses (CRs) to trauma-related cues. If individuals also experience pain to cues previously paired with, but not anymore inflicting nociceptive stimulation (CSs), conditioning could also explain re-experiencing of pain. Sixty-five participants underwent classical conditioning, where painful electrocutaneous stimulation and aversive film-clips served as unconditioned stimuli (USs) in a 2 (pain/no pain) x 2 (aversive/neutral film) design. CSs were neutral pictures depicting contextual details from the films. One day later, participants were re-exposed to CSs during a memory-triggering-task (MTT). We assessed pain-CRs by self-report and an fMRI-based marker of nociceptive pain, the neurologic pain signature (NPS); and recorded spontaneous daily-life pain-intrusions with an e-diary. During conditioning, pain-signaling CSs elicited more self-reported-pain and NPS-responses than no-pain-signaling CSs. Possibly because the aversive-film masked differences in participants’ responses to pain-signaling vs. no-pain-signaling CSs, pain-CRs during acquisition only emerged within the neutral-film condition. When participants were re-exposed to CSs during MTT, self-reported-pain-CRs during the neutral-film condition and NPS-CRs during the aversive-film condition persisted. Importantly, participants with stronger pain-CRs showed a greater probability and severity of experiencing spontaneous pain intrusions during daily-life. Our data support that pain can emerge as a CR with emotional and sensory components. Classical conditioning presents a possible mechanism explaining pain-intrusions, and more broadly, pain experienced without nociceptive input.