Attention and Nocebo Hyperalgesia: Testing a Novel Virtual Reality Attention Bias Modification Paradigm

Nocebo effects in pain (nocebo hyperalgesia) have received significant attention recently, with negative expectancies and anxiety proposed to be explanatory factors. While both expectancy and anxiety can bias attention, attention has been rarely explored as a potential mechanism involved in nocebo hyperalgesia. The present study aimed to explore whether attention bias modification (ABM) using an immersive, ecologically valid VR paradigm successfully induced attention biases (AB) and subsequently influenced nocebo hyperalgesia. One-hundred and two healthy participants were randomised in a 2 (AB training: towards vs. away from pain) x 2 (nocebo condition: nocebo vs. control) design. Pain-related AB was successfully changed by the VR paradigm as measured by reaction time and gaze, with moderate to large effects. Participants then completed either a nocebo instruction and conditioning procedure (nocebo paradigm) or a matched control procedure. The primary outcome was self-reported pain intensity. Secondary outcomes were attention bias and self-reports of expectancy, anticipatory anxiety, and state anxiety. The nocebo paradigm induced significantly greater pain expectancy, anticipatory anxiety and pain intensity during the test phase for the nocebo group compared to control. Pain expectancy also fully mediated the effect of the nocebo group on nocebo hyperalgesia and anticipatory anxiety in separate models. ABM did not, however, affect nocebo hyperalgesia or pain expectancy, casting doubt on the potential for ABM to inoculate against nocebo hyperalgesia. Unexpected effects of ABM were observed for state anxiety and anticipatory anxiety, whereby training away from pain exacerbated each, which necessitates further exploration. PERSPECTIVE: This article tests the efficacy of a novel attention bias modification paradigm, designed in virtual reality, for inducing pain-related biases, and whether these biases exacerbate or inoculate against nocebo hyperalgesia. While pain-related biases were successfully induced, there was no relationship with the strength of induced nocebo hyperalgesia.