The role of learning mechanisms on pain perception and chronification.

Non-specific chronic back pain (CBP) constitutes a tremendous social and psychological impact for patients, but also a major economic burden. In chronic pain, the biological warning function of acute pain is often missing. Although, altered pain-related learning mechanisms are thought to contribute to the development and maintenance of chronic pain, experimental research is scarce. For recovery, it is important to "unlearn" previously acquired pain-related associations through extinction learning processes and to develop robust extinction memory. Extinction learning might further be influenced by stress. Thus, this thesis investigated pain-related acquisition and extinction learning on one study day, and the influence of pharmacologically induced stress via oral hydrocortisone administration in a randomized placebo-controlled, double-blind design on the retrieval of extinction memory and the reinstatement of pain-related associations one day later in N = 62 patients with CBP and N = 61 healthy, pain-free, age- and sex-matched volunteers (healthy controls, HCs). In a two-day classical differential conditioning paradigm, geometric figures served as conditioned stimuli (CS) that predicted the appearance (threat cue, CS+) or absence (safety cue, CS-) of an unconditioned heat pain stimulus (US). Self-reported valence ratings were assessed as a behavioral measure for implicit evaluative learning, while contingency ratings covered its explicit aspect. Skin conductance responses (SCRs) were recorded as a physiological measure. Valence ratings of study day 1 indicate significantly impaired pain-related threat and safety learning in patients with CBP. SCRs of study day 2 showed hydrocortisone-induced reinstatement of pain-related associations in HCs, but not in patients. In contrast, placebo-treated patients revealed reinstatement of pain-related associations in their SCRs, while placebo-treated HCs did not. Thus, patients seem to have an increased relapse potential, which, together with the impaired pain-related threat and safety learning, may significantly contributes to the maintenance of the chronic pain state and complicates its treatment. Enhanced treatment approaches are thus strongly needed to help patients develop more robust extinction memory and reduce the risk of relapse. The unequal effects of hydrocortisone emphasize the complexity of the non-specific CBP disease and the need for additional research to unravel its different psychological, pathophysiological, and neural underpinnings.