人類疼痛特有習慣化的大腦特徵

Abstract

習慣化是一個自然的止痛歷程，但其背後的中樞神經機制仍有許多未知的部分。先前的研究展示了長期痛覺習慣化（給予重複的痛刺激多天後疼痛反應減少）發生在重複刺激的部位以及未接受刺激的部位，但這種現象是否出現在短期的痛覺習慣化則仍不清楚。為了解此議題，我們招募了十六位健康的受試者，在他們左前臂腹側 (left volar forearm) 施予疼痛刺激時使用功能性磁振造影來研究腦部相關的反應。我們藉由比較施予重複痛刺激前後的行為及影像反應來評估痛覺習慣化，且進一步與重複的無痛刺激所引起的習慣化相比以得知痛覺習慣化的程度。研究結果顯示，相對於長期痛覺習慣化，短期的痛覺習慣化僅發生在接受刺激的部位。前扣帶迴皮質 (perigenual anterior cingulate cortex) 的活動在痛覺習慣化中是特有的。此外，前扣帶迴皮質與前腦島 (anterior insular cortex) 以及外側前額葉皮質 (lateral prefrontal cortex) 之間的功能性連結和痛覺習慣化的程度有正相關。這些發現顯示短期痛覺習慣化牽涉到獨特的中樞神經元素，包含了與止痛、痛覺處理以及調節注意力相關的腦區。

Habituation is a natural analgesic process, but the underlying central mechanisms are largely unknown. Prior studies have shown that long-term pain habituation (i.e., reduced responses to repetitive painful stimuli applied over several days) occurred in both the repetitively stimulated site and non-stimulated sites, but whether this phenomenon also exists in short-term pain habituation process (i.e., adaptation after a period of repetitive painful stimuli) remains unclear. To address these issues, we recruited sixteen healthy subjects and used functional MRI to investigate neural substrates underlying short-term pain habituation during repetitive painful stimuli applied to the left volar forearm. Pain-induced habituation was evaluated by comparing behavioral and neuroimaging responses before and after stimulation, and the extent of habituation was further analyzed against the habituation effects induced by repetitive nonpain stimuli. Different from long-term pain habituation, short-term pain habituation only developed in the stimulated site. Importantly, activity in the perigenual anterior cingulate cortex (pACC) was unique to the short-term habituation of pain. Moreover, the strength of functional connectivity from the pACC to the anterior insula and the lateral prefrontal cortex was parametrically associated with the degree of pain habituation. These findings suggest that short-term habituation to repetitive noxious stimuli involves a distinct central component, consisting of areas involved in antinociception, nociceptive processing, and attentional modulation.