Background & Aims
Expectations substantially affect human perception to aversive stimuli (Benedetti et al, 2018), such as pain (Atlas and Wager, 2012) and itch (Meeuwis et al, 2020). While the neural mechanisms underlying pain modulation by expectations have been extensively studied, the corresponding mechanisms for itch expectation remains unclear. The difference in the cerebral processing associated with these two types of aversive stimulation, particularly at the cognitive level, remains incompletely understood. Clinically, there exist complex interactions between pain and itch perceptions, but whether expectations for pain bias itch perception, and vice versa, remain unknown. The present study aimed to (1) elucidate the neural basis underlying how itch expectations influence an individual’s itch sensation, (2) examine the similarities and differences between itch and pain expectancy effects, and (3) explore interactions between itch and pain at the cognitive level (Weng et al, 2022a, 2022b).
Methods
We used functional MRI to record participants’ brain responses when they performed two kinds of stimulus expectancy task for pain and itch stimulation: same-modality (SM) and cross-modality (CM) task. Participants first underwent a conditioning session which consisted of SM tasks (that is, the type of expected stimulation was congruent with the type of applied stimulus; e.g. an itch cue followed by an itch stimulus) and they learned the cue-outcome contingencies. This was followed by the test session encompassing both SM and CM tasks. In a CM task, the anticipated stimulation was incongruent with the applied stimulation in terms of stimulus modality (e.g. an itch cue followed by a painful stimulus, and vice versa). The goal of our manipulations was threefold: (1) to maintain participants’ beliefs about the expected pain or itch intensity acquired during the conditioning session, and (2) to induce the expectancy effects of itch or pain. Imaging data were analyzed using SPM12.
Results
As expected, we found that, in the SM condition, pain expectation significantly modulated participants’ perception to pain, which is consistent with previous research (Shih et al, 2019). Similar to pain, itch expectation also significantly modulated participants’ perception to itch. For both pain and itch, positive expectation (expectation for decreased stimulus intensity) reduced participants’ perception, whereas negative expectation (expectation for increased stimulus intensity) enhanced participants’ perception. Interestingly, in the CM condition, pain expectation did not significantly affect the perception to itch, and vice versa. Preliminary fMRI analyses revealed that pain and itch stimulation elicited common activation in a set of brain regions, including the prefrontal cortex, motor area, and insula.
Conclusions
Our findings suggest that, at the behavioral level, itch expectancy exhibits similar effects on itch perception as pain does. Although itch and pain are both aversive stimuli, we observe no cross-modality interaction between these two types of stimulation. This result suggests that the stimulus expectancy effects of pain and itch are highly selective in the sensory-discriminative aspects, which improves current understanding of itch vs pain processing at the cognitive level. We are increasing the number of our participants and in the near future will analyze participants’ fMRI data to disclose the difference in neural mechanisms underlying the stimulus expectancy effects between pain and itch. Insights obtained from this study will improve current understanding about the interaction between pain and itch in clinical conditions.
References
Atlas LY, Wager TD. How expectations shape pain. Neurosci Lett. 2012;520(2):140-8
Benedetti F, Piedimonte A, Frisaldi E. How do placebos work? Eur J Psychotraumatol. 2018;9(Suppl 3):1533370.
Ikoma A, Handwerker H, Miyachi Y, Schmelz M. Electrically evoked itch in humans. Pain. 2005;113(1-2):148-54.
Meeuwis SH, van Middendorp H, van Laarhoven AIM, van Leijenhorst C, Pacheco-Lopez G, Lavrijsen APM, Veldhuijzen DS, Evers AWM. Placebo and nocebo effects for itch and itch-related immune outcomes: A systematic review of animal and human studies. Neurosci Biobehav Rev. 2020;113:325-337.
Shih YW, Tsai HY, Lin FS, Lin YH, Chiang CY, Lu ZL, Tseng MT. Effects of Positive and Negative Expectations on Human Pain Perception Engage Separate But Interrelated and Dependently Regulated Cerebral Mechanisms. J Neurosci. 2019;39(7):1261-1274.
Weng L, Peerdeman KJ, Della Porta D, van Laarhoven AIM, Evers AWM. Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations? Pain. 2022a;163(3):548-559.
Weng L, van Laarhoven AIM, Peerdeman KJ, Evers AWM. Induction and generalization of nocebo effects on itch. Exp Dermatol. 2022b;31(6):878-889.
Presenting Author
Tsu-Chun Yang
Poster Authors
Tsu-Chun Yang
BS
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, NTU,
Lead Author
Hsin-Yun Tsai
PhD
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, NTU,
Lead Author
Ming-Tsung Tseng
MD
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, NTU,
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Itch