Department of Neurosurgery, Neurosurgery Pain Research Institute, School of Medicine, Johns Hopkins University, Baltimore, United States.
Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, United States.
Elife. 2021 Apr 23;10:e64506. doi: 10.7554/eLife.64506.
In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22, and histamine, which activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.
在人类中，皮内给予β-丙氨酸（ALA）和牛肾上腺髓质肽 8-22（BAM8-22）会引起瘙痒感。目前，尚不清楚这些致痒原分别激活哪些人类背根神经节（DRG）神经元的受体 MRGPRD 和 MRGPRX1，也不清楚这些致痒原在灵长类动物中激活哪些皮肤传入纤维。原位杂交研究表明，MRGPRD 和 MRGPRX1 在 TRPV1+人类 DRG 神经元的亚群中共表达。在非人类灵长类动物（）的电生理记录中，多模式 C 纤维伤害感受器的亚型优先被 ALA 和 BAM8-22 激活，且有显著重叠。当致痒原 ALA、BAM8-22 和组胺（激活不同的 C 纤维传入纤维亚型）联合给药时，人类志愿者报告的瘙痒和痛觉感觉与单一致痒原诱导的感觉相似。我们的结果提供了灵长类动物和啮齿动物之间瘙痒处理差异的证据，不支持瘙痒和疼痛编码的空间对比理论。
