The Role of Pain Expectations in the Development of Secondary Pinprick Hypersensitivity: Behavioral-Neurophysiological Evidence and the Role of Pain-Related Fear

Secondary mechanical hypersensitivity, a common symptom of neuropathic pain, reflects increased responsiveness of nociceptive pathways and can be induced temporarily in healthy volunteers using high-frequency electrical stimulation of the skin. Expectations modulate acute pain perception and fear of pain has been shown to attenuate and amplify the placebo and nocebo effects respectively. However, the role of expectations and fear in the development of mechanical secondary hypersensitivity remains unclear. The modulatory role of fear and expectations in the development of mechanical secondary hypersensitivity remains so far mainly correlational. Here, we randomly assigned healthy participants (women) to a placebo, nocebo, or control group. In the experimental groups, participants' expectations of pain were manipulated using verbal suggestions accompanied by an inert treatment. Fear of pain was evaluated both in terms fear of pain and via questionnaires. Sensitivity to mechanical stimulation was assessed by self-reported pinprick ratings before and after high-frequency stimulation; pinprick-evoked potentials elicited by the stimulation were recorded. The placebo group developed the least mechanical secondary hypersensitivity (smaller proximal-distal spread) while the nocebo group developed the most, but only when outliers were excluded. Higher expectations of pain predicted a greater development of mechanical secondary hypersensitivity. Anticipatory pain-related fear only mediated the relationship between unpleasantness expectations and perceived pinprick unpleasantness. Dispositional fear of pain moderated the relationship between expectations and the perceived intensity and unpleasantness of pinpricks. No group differences were observed in pinprick-evoked potentials. We provide preliminary evidence that both expectations and fear impact the development of mechanical secondary hypersensitivity. Perspective Expectations of pain may influence the development of secondary mechanical hypersensitivity. This effect is moderated by dispositional fear of pain and partially mediated by situational fear of pain.