探討預期調節疼痛之機制中的情緒成分：功能性磁振造影實驗

Abstract

人類的知覺會受到認知和情緒因素影響。在痛覺方面，負向預期（預期疼痛增加）和正向預期（預期疼痛減少）分別會加劇和緩解所經歷的疼痛。然而，預期所誘發之疼痛調控其心理機制尚不清楚。在一個以提示作為基礎的預期派典（cue-based expectancy paradigm）結合功能性磁振造影技術（functional magnetic resonance imaging technology）的實驗中，三十一名受試者（包括男性和女性）使用情緒調節（emotion regulation）策略以降低疼痛預期所引發的情緒。皮膚電傳導活動（electrodermal activity）數據顯示，相較於受試者們自然經歷預期所引發的情緒，當他們使用情緒調節策略以減少這些情緒時，負向預期及正向預期所引起的皮膚電導反應（skin conductance response）均會減少，這表示情緒調節策略能有效操弄預期相關情緒。而自我報告的情緒評分更進一步發現，受試者透過情緒調節策略能夠降低負向預期引起的焦慮程度、以及降低正向預期引起的愉悅程度。重要的是，當受試者使用情緒調節策略時，負向預期所誘發的的增痛效果和正向預期所誘發的減痛效果都顯著減少了，並且，此預期誘發之疼痛調控效果的減少程度能夠被情緒評分的變化所預測，這代表了情緒在預期誘發之疼痛調控機制中的關鍵作用。功能性磁振造影（functional magnetic resonance imaging）結果顯示，杏仁核（amygdala）活化程度反應了負向預期所引起的焦慮程度，而內側眶額皮質（medial orbitofrontal cortex）則會紀錄正向預期所引起的主觀愉悅感。在行為和神經層面上發現了預期誘發之疼痛調控機制中的情緒成分後，此研究進一步探討了預期是如何透過這些情緒成分去調控痛覺。第一項機制涉及了預期與感官輸入（sensory input）之間的訊號整合。貝葉斯模型選擇（Bayesian model selection）的結果支持「情緒性整合模型（emotion integration model）」——預期和感官輸入的整合是根據其相對的情緒經驗進行加權——勝過「準確性整合模型（precision integration model）」——預期和感官輸入的整合是依據其相對的準確性進行加權。影像分析近一步發現，負向預期和感官輸入之間的情緒性整合是透過杏仁核和前扣帶皮質（anterior cingulate cortex）兩個腦區之間的功能性連結（functional connectivity）所進行，而正向預期相關的情緒性整合則是由內側眶額皮質和海馬迴（hippocampus）間之連結所負責。第二項機制涉及情緒對學習相關機制的影響，此實驗發現，負向預期所引期的焦慮會抑制前扣帶皮質的預測誤差（prediction error）神經訊號以阻礙負向預期的更新，使負向預期所誘發的的增痛效果得以一直存在。本研究證實了情緒在預期調控人類痛覺此過程中的重要角色。

Human perceptions are substantially shaped by cognitive and emotional factors. In terms of pain perception, negative expectations (i.e., expecting increased pain) and positive expectations (i.e., expecting decreased pain) respectively exacerbate and alleviate experienced pain. However, the psychological mechanisms underlying this modulation are not fully understood. In a cue-based expectancy paradigm, thirty-one participants (both male and female) were instructed to employ emotion regulation (ER) strategies to manage expectancy-elicited emotions. Electrodermal data showed that both negative and positive expectancy-induced skin conductance responses decreased when participants used ER strategies to downregulate their emotions, compared to when they experienced these emotions naturally, suggesting that ER strategies were effective in regulating expectancy-related emotional responses. Self-reported emotion ratings further revealed that participants were able to decrease anticipatory anxiety associated with negative expectations and lessen anticipatory pleasantness associated with positive expectations through ER strategies. Importantly, the pain-enhancing effect of negative expectations and the pain-reducing effect of positive expectations were both diminished when participants used ER strategies. This reduction in expectancy effects was predicted by changes in anticipatory emotions, indicating the crucial role of emotions in pain modulation by stimulus expectation. The functional MRI data revealed that the individual anticipatory anxiety for negative expectations was encoded by the amygdala, while the subjective pleasantness for positive expectations was tracked by the medial orbitofrontal cortex (mOFC). After identifying the emotional components at both behavioral and neural level, the study then explored how these emotional components contribute to expectancy-induced pain modulation. The first mechanism involves integrating prior expectations with incoming sensory inputs. Bayesian model selection favored an emotion integration model, where prior expectations and sensory inputs are weighted by their relative emotional experiences, rather than a precision integration model, which weights the integration according to the precision of the expectancy and sensory information. This finding was supported by functional coupling between the amygdala and anterior cingulate cortex (ACC) for negative expectations and between the mOFC and hippocampus for positive expectations. The second mechanism pertains to emotional modulation on prediction error processing. Anticipatory anxiety appeared to hinder the updating of negative expectations by suppressing prediction error signals in the ACC. Overall, this study highlights the significant role of emotions in shaping pain experiences influenced by stimulus expectancy.