本文是Quanta Magazine播客《The Joy of Why》的一期節目逐字稿，主持人Janna Levin與哥倫比亞大學Zuckerman研究所的神經科學家Ishmail Abdus-Saboor進行了深入對談。討論圍繞皮膚作為感覺器官如何傳遞疼痛與愉悅展開，涵蓋了痛覺的演化意義、實驗室中量化疼痛與愉悅的困難，以及觸覺作為社會和情感信號的重要性。Abdus-Saboor分享了自己從費城少年時期在家中三樓養殖數百隻小龍蝦做再生實驗的經歷，到進入分子生物學和神經科學領域的學術歷程。（關鍵數字： a year）
在疼痛研究方面，節目介紹了兩項獲得2021年諾貝爾獎的突破性發現：David Julius發現的辣椒素受體TRPV1（同時也是熱感受器）以及Ardem Patapoutian發現的機械力感受通道Piezo1和Piezo2。Abdus-Saboor強調，至今科學界仍然缺乏疼痛的客觀生物標記物，臨床上只能依賴患者的主觀報告。節目還討論了巴基斯坦一個完全無法感受疼痛的家族——其基因突變位於Nav1.7鈉離子通道——以及安慰劑效應如何通過內源性鴉片系統真實地調節疼痛感知，揭示了心理因素影響疼痛的生理基礎。
在愉悅觸覺與社會行為方面，Abdus-Saboor介紹了他實驗室發現的一組表達MRGPRB4基因的神經元，這些神經元專門回應撫摸式的社交觸覺，並能觸發大腦獎賞中心的多巴胺釋放。他還詳細描述了裸鼴鼠這一非凡物種——牠們幾乎不感受疼痛、不易患癌、壽命可達30至40年且無明顯衰老跡象，並以高度社會化的蜂群式群落生活，以觸覺作為主要感官。Abdus-Saboor的團隊正在探索觸覺如何緩解壓力和焦慮，以及眶額皮質如何根據情境將同樣的觸覺信號解讀為愉悅或厭惡，期望未來能通過靶向皮膚神經元來治療大腦相關疾病。
This episode of The Joy of Why podcast features a conversation between host Janna Levin and Columbia University neuroscientist Ishmail Abdus-Saboor about the neuroscience of touch, pain, and pleasure. Abdus-Saboor traces his path from a childhood fascination with animals in Philadelphia — where he ran a year-long crayfish regeneration experiment on his family's third floor — to his current research on the skin-brain axis. The discussion highlights how pain remains deeply mysterious: there is still no objective biomarker for it, the boundary between physical and psychological pain is blurred, and researchers must rely on careful behavioral observation to infer what animals experience, raising significant ethical questions about animal experimentation.
The episode covers landmark molecular discoveries that have transformed pain research, including the 2021 Nobel Prize-winning identification of TRPV1 (a receptor for both capsaicin and noxious heat, discovered by David Julius) and Piezo1/Piezo2 (mechanosensory channels discovered by Ardem Patapoutian). At least 15 distinct classes of sensory neurons have now been characterized. Abdus-Saboor also discusses the case of a Pakistani family with Nav1.7 mutations who feel no pain at all, the placebo effect's powerful action through endogenous opioid circuits, and the problematic overlap between pain relief and addiction pathways. He envisions future therapies that could selectively eliminate the emotional suffering component of pain while preserving its protective sensory function.
On the pleasure side of touch, Abdus-Saboor describes a population of neurons expressing the gene MRGPRB4 that specifically respond to gentle stroking and trigger dopamine release in the brain's reward center, forming a dedicated social-reward pathway distinct from pain circuits. His lab uses optogenetics — genetically engineering mice to respond to blue light — to precisely activate these neurons and study how context determines whether identical touch is perceived as pleasant or aversive, with the orbitofrontal cortex emerging as a key integration hub. The conversation also explores naked mole rats, remarkable mammals that are nearly pain-insensitive, cancer-resistant, show no signs of aging, and live in enormous eusocial colonies governed by a single queen, relying predominantly on touch for communication. Abdus-Saboor hopes that understanding their cooperative, touch-driven societies and the molecular mechanisms underlying social touch may ultimately inform treatments for stress, anxiety, and depression in humans.