本文是Quanta Magazine播客《The Joy of Why》的一期节目逐字稿，主持人Janna Levin与哥伦比亚大学Zuckerman研究所的神经科学家Ishmail Abdus-Saboor进行了深入对谈。讨论围绕皮肤作为感觉器官如何传递疼痛与愉悦展开，涵盖了痛觉的演化意义、实验室中量化疼痛与愉悦的困难，以及触觉作为社会和情感信号的重要性。Abdus-Saboor分享了自己从费城少年时期在家中三楼养殖数百只小龙虾做再生实验的经历，到进入分子生物学和神经科学领域的学术历程。（关键数字： a year）
在疼痛研究方面，节目介绍了两项获得2021年诺贝尔奖的突破性发现：David Julius发现的辣椒素受体TRPV1（同时也是热感受器）以及Ardem Patapoutian发现的机械力感受通道Piezo1和Piezo2。Abdus-Saboor强调，至今科学界仍然缺乏疼痛的客观生物标记物，临床上只能依赖患者的主观报告。节目还讨论了巴基斯坦一个完全无法感受疼痛的家族——其基因突变位于Nav1.7钠离子通道——以及安慰剂效应如何通过内源性鸦片系统真实地调节疼痛感知，揭示了心理因素影响疼痛的生理基础。
在愉悦触觉与社会行为方面，Abdus-Saboor介绍了他实验室发现的一组表达MRGPRB4基因的神经元，这些神经元专门回应抚摸式的社交触觉，并能触发大脑奖赏中心的多巴胺释放。他还详细描述了裸鼹鼠这一非凡物种——牠们几乎不感受疼痛、不易患癌、寿命可达30至40年且无明显衰老迹象，并以高度社会化的蜂群式群落生活，以触觉作为主要感官。Abdus-Saboor的团队正在探索触觉如何缓解压力和焦虑，以及眶额皮质如何根据情境将同样的触觉信号解读为愉悦或厌恶，期望未来能通过靶向皮肤神经元来治疗大脑相关疾病。
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.