Cognitive bias modification for interpretation mitigates nocebo hyperalgesia

Interpretation bias, or the extent to which one interprets ambiguous information as pain-related, has been previously shown to be associated with increased pain severity. The current study tested whether modifying interpretation biases influenced nocebo hyperalgesia. Participants were randomised to receive cognitive bias modification for interpretation (CBM-I) to induce biases either towards pain-related interpretations or towards benign interpretations. Participants then completed a nocebo instruction and conditioning induction, where a sham TENS was paired with increased thermal pain stimuli, or matched control condition. A nocebo test phase followed where TENS and no-TENS trials were paired with identical thermal pain, such that any difference would be indicative of nocebo hyperalgesia. Results found reliable evidence of nocebo hyperalgesia, which was mediated by pain expectancy. Interpretation bias was successfully manipulated, as individuals who received CBM-I training towards pain showed greater interpretation bias than those who received benign training. Critically, as hypothesized, participants who received CBM-I training towards pain exhibited significantly larger nocebo hyperalgesia than the benign training group. Furthermore, a serial mediation model indicated that CBM-I increased interpretation bias towards pain, which led to increased pain expectancy, which in turn increased nocebo hyperalgesia, suggesting a causal role of interpretation bias in nocebo hyperalgesia. These results suggest that interpretation biases could be a previously unrecognised mechanism involved in exacerbating the experience of nocebo hyperalgesia. Perspective This study demonstrations that training pain-related interpretations of ambiguous information, when compared to training benign interpretations, amplifies experienced nocebo hyperalgesia by increasing nocebo expectancy. Taken together, findings identify reducing pain-related interpretations through cognitive bias modification as a potential psychological target to reduce nocebo-related pain in clinical contexts.