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'First pain' in humans: convergent and specific forebrain responses

机译：人类的“初次疼痛”：收敛和特定的前脑反应

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Background Brief heat stimuli that excite nociceptors innervated by finely myelinated (Aδ) fibers evoke an initial, sharp, well-localized pain ("first pain") that is distinguishable from the delayed, less intense, more prolonged dull pain attributed to nociceptors innervated by unmyelinated (C) fibers ("second pain"). In the present study, we address the question of whether a brief, noxious heat stimulus that excites cutaneous Aδ fibers activates a distinct set of forebrain structures preferentially in addition to those with similar responses to converging input from C fibers. Heat stimuli at two temperatures were applied to the dorsum of the left hand of healthy volunteers in a functional brain imaging (fMRI) paradigm and responses analyzed in a set of volumes of interest (VOI). Results Brief 41°C stimuli were painless and evoked only C fiber responses, but 51°C stimuli were at pain threshold and preferentially evoked Aδ fiber responses. Most VOI responded to both intensities of stimulation. However, within volumes of interest, a contrast analysis and comparison of BOLD response latencies showed that the bilateral anterior insulae, the contralateral hippocampus, and the ipsilateral posterior insula were preferentially activated by painful heat stimulation that excited Aδ fibers. Conclusions These findings show that two sets of forebrain structures mediate the initial sharp pain evoked by brief cutaneous heat stimulation: those responding preferentially to the brief stimulation of Aδ heat nociceptors and those with similar responses to converging inputs from the painless stimulation of C fibers. Our results suggest a unique and specific physiological basis, at the forebrain level, for the "first pain" sensation that has long been attributed to Aδ fiber stimulation and support the concept that both specific and convergent mechanisms act concurrently to mediate pain.
机译：背景技术短暂的热刺激激发细微有髓（Aδ）纤维支配的伤害感受器，引起最初的，尖锐的，局部性疼痛（“第一痛”），这与延迟的，较弱的，更长的钝痛有关，后者是由伤害感受器支配的无髓（C）纤维（“第二痛”）。在本研究中，我们解决的问题是，除了对C纤维的聚合输入具有类似响应的那些结构之外，短暂的，有害的热刺激是否会刺激皮肤Aδ纤维激活一组独特的前脑结构。在功能性脑成像（fMRI）范例中，将两个温度下的热刺激应用于健康志愿者的左手背，并在一组感兴趣的体积（VOI）中分析响应。结果短暂的41°C刺激无痛且仅引起C纤维反应，而51°C刺激处于疼痛阈值且优先引起Aδ纤维反应。大多数VOI都对两种刺激强度都有反应。然而，在感兴趣的体积内，BOLD响应潜伏期的对比分析和比较显示，双侧前绝缘，对侧海马和同侧后绝缘优先通过疼痛的热刺激激活Aδ纤维来激活。结论这些发现表明，两组前脑结构介导了短暂的皮肤热刺激引起的最初的尖锐疼痛：优先响应Aδ热伤害感受器的短暂刺激的那些和对无痛C纤维刺激的聚合输入具有相似响应的那些。我们的结果表明，在前脑水平上，长期以来一直归因于Aδ纤维刺激的“第一痛”感觉具有独特而特定的生理基础，并支持特定和收敛机制同时起作用来介导疼痛的概念。

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