The effect of unpredictability on the perception of pain: a systematic review and meta-analysis

Despite being widely assumed, the worsening impact of unpredictability on pain perception remains unclear because of conflicting empirical evidence, and a lack of systematic integration of past research findings. To fill this gap, we conducted a systematic review and meta-analysis focusing on the effect of unpredictability on pain perception. We also conducted meta-regression analyses to examine the moderating effect of several moderators associated with pain and unpredictability: stimulus duration, calibrated stimulus pain intensity, pain intensity expectation, controllability, anticipation delay, state and trait negative affectivity, sex/gender and age of the participants, type of unpredictability (intensity, onset, duration, location), and method of pain induction (thermal, electrical, mechanical pressure, mechanical distention). We included 73 experimental studies with adult volunteers manipulating the (un)predictability of painful stimuli and measuring perceived pain intensity and pain unpleasantness in predictable and unpredictable contexts. Because there are insufficient studies with patients, we focused on healthy volunteers. Our results did not reveal any effect of unpredictability on pain perception. However, several significant moderators were found, ie, targeted stimulus pain intensity, expected pain intensity, and state negative affectivity. Trait negative affectivity and uncontrollability showed no significant effect, presumably because of the low number of included studies. Thus, further investigation is necessary to clearly determine their role in unpredictable pain perception.