Reward for Pain: Hyperalgesia and Allodynia Induced by Operant Conditioning: Systematic Review and Meta-Analysis

Learning processes have been discussed in the context of pain chronicity for decades. Particularly, operant conditioning has been used to experimentally induce and modulate pain in healthy humans. In this systematic review and meta-analysis, research findings on pain facilitation (hyperalgesic effect) and pain elicitation (allodynic effect) are evaluated. The review was performed according to the PRISMA guideline and an a priori published protocol. Nine databases were searched for relevant publications: PubMed, Cochrane Register of Controlled Trials (CENTRAL), Web of Science, ScienceDirect, EBSCO, PsycINFO, MEDLINE, PsycARTICLES, and CINAHL. Studies were included if they investigated pain-free humans, exposed to an operant conditioning procedure of pain. Two independent assessors screened publications against eligibility criteria and assessed the risk of bias with the Cochrane risk of bias scale. A total of 3155 records were screened, of which 8 were included in the qualitative (401 participants) and 5 into the quantitative (110 participants) synthesis. Results showed that hyperalgesic (standardized mean difference = -0.80, 95% confidence interval = -1.33 to -0.27, P = .003) and allodynic effects (standardized mean difference = -1.27, 95% confidence interval = -2.46 to -0.08, P = .04) can be induced in healthy humans, indicating that pain can be shaped by contingencies of reinforcement. However, the uncertainty of the effect is relatively high, mostly owing to the small number of included studies, demand characteristics, and the risk of bias. This is especially relevant for studies on allodynic effects where the decrease in nociception should be more rigorously controlled. PERSPECTIVE: Operant conditioning can be a mechanism of pain chronicity. All experimental studies investigating this hypothesis have been identified and summarized. It has been demonstrated that allodynic and hyperalgesic effects can be induced by operant conditioning.