Chapter 4 – Experimental learning 111 Introduction It has been demonstrated that negative expectations regarding treatment outcomes may aggravate pain symptoms 1–4, a phenomenon termed nocebo hyperalgesia 2,5. In experimental research, nocebo hyperalgesia is defined as a significant increase in pain following a nocebo treatment, relative to no-treatment or a control treatment. Negative expectations may enhance aversive side-effects 6 or produce deleterious effects on pain recovery 7. Classical conditioning is an important underlying mechanism of nocebo hyperalgesia 8–10. In conditioning paradigms, the pairing of a conditioned stimulus (CS; e.g., an inert treatment) with an unconditioned stimulus (US; e.g., surreptitiously increased pain) leads to a learned association 11,12. As a result of this learned association, an inert treatment can evoke increases in perceived pain 10. The vast majority of nocebo studies induce hyperalgesia by use of conditioning with continuous reinforcement (100% pairing of CS and US). In a more ambiguous type of conditioning with partial reinforcement, stimuli are paired in less than 100% of trials, thus the contingency between pain and an inert nocebo treatment is more variable. Partial reinforcement is of particular clinical interest due to its variable nature, which resembles the more ambiguous and inconsistent learning that may occur in clinical settings 13. Partial reinforcement conditioning has been successfully used in fear research 14 and was recently also implemented in nocebo research 15. Colagiuri and colleagues compared continuous and partial reinforcement schedules and found that nocebo hyperalgesia can be induced through partial reinforcement 15. Additionally, Colagiuri and colleagues 15 investigated the consistent finding from fear studies that partial reinforcement conditioning shows more resistance to extinction than continuous reinforcement 14,16,17. In contrast to findings in other fields of research 14, extinction was unsuccessful in attenuating nocebo hyperalgesia
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