The influence of expectations and attention on conditioned pain modulation: A systematic review and meta-analysis

Conditioned pain modulation (CPM) is a psychophysical experimental measure of endogenous pain inhibition in humans. Within this paradigm, one noxious stimulus, the conditioning stimulus (CS), reduces the pain perception from another heterotopic noxious stimulus, the test stimulus (TS). Cognitive processes are known to influence pain perception and might impact the underlying mechanisms of CPM. This systematic review and meta-analysis synthesizes the existing scientific literature addressing the influence of cognitive factors, namely, expectations and attention on CPM. Four electronic databases were searched to identify relevant literature. Risk of bias and quality of evidence were assessed according to two modified Newcastle-Ottawa Scales and the GRADE approach, respectively. Twenty-four articles were included. Qualitative analysis showed more efficient CPM when pain relief is expected, and an association between intrinsic attention to pain and reduced CPM. Although the evidence is not unanimous, meta-analyses showed that CPM is more efficient when attention is directed towards the CS versus the TS, and is not influenced by distraction. In conclusion, while CPM seems robust to attentional distraction, expectations and attentional focus appear to influence CPM. However, the evidence is limited and conflicting and warrants further study in order to prevent cognitive confounding and enhance mechanistic understanding.