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

Abstract

Psychological trauma is typically accompanied by physical pain, and posttraumatic stress disorder (PTSD) often co-occurs with chronic pain. Clinical reports suggest that pain in the aftermath of trauma may be part of a re-experiencing symptomatology. Previously, we demonstrated that classical conditioning can underlie visual re-experiencing since intrusions appear to occur as conditioned responses (CRs) to trauma-related cues. Possibly, classical conditioning also plays a role in re-experiencing of pain. However, this hypothesis has so far remained untested. Sixty-five participants underwent classical conditioning, where painful electrical stimulation and highly aversive film-clips served as unconditioned stimuli (USs) in a 2 (pain/no pain) x 2 (aversive/neutral film) design. Conditioned stimuli (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). Pain-CRs were assessed by self-report and an fMRI-based marker of nociceptive pain, the neurologic pain signature (NPS).During conditioning, pain-signaling CSs elicited more self-reported pain and NPS responses than no-pain-signaling CSs. Self-reported pain-CRs but not NPS CRs recurred 24h later when participants were re-exposed to CSs during MTT. Both during acquisition and MTT, the aversive affective film-context blurred the difference in participants´ pain-reports to pain-signaling and no-pain-signaling CSs.Our data support the hypothesis that pain can emerge as a classically conditioned response. Pain as a CR to pain-signaling cues could represent an instance of pain re-experiencing in PTSD. Possibly, this mechanism may perpetuate pain beyond tissue healing and thereby explain the comorbidity between chronic pain and PTSD.

Pain cannot be a conditioned response

“…The function of the CS is to inform the organism that something is about to occur. 4,5 The procedure used in the study by Franke et al 2 closely parallels that used in aversive conditioning. In the very large body of research on aversive conditioning, the conditioned response is, as mentioned above, always fear or its psychological approximation.…”

“…Years of research has implicated exaggerated subjective fear to CS as a core feature of psychiatric disorders, such as posttraumatic stress disorder and their treatment. [2][3][4] In this vein, if fear without actual danger can be a CR, why not also pain without actual nociceptive input?…”

Reply to Quintner

“…We appreciate Dr. Quintner's thought-provoking comments 15 to our article 6 and are grateful for the opportunity to clarify some issues.…”

Can pain be re-experienced as a conditioned response?

“…This is the question that Franke and colleagues set out to test in a research article published in this issue of PAIN. 4 Their study was inspired by research on post-traumatic stress disorder (PTSD). Indeed, patients with PTSD often report reexperiencing the traumatic event as if it was happening again, and these flashbacks often include painful sensations if these were part of the original traumatic event.…”

“…This is the question that Franke and colleagues set out to test in a research article published in this issue of PAIN . 4…”