Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nat Commun. 2020 Mar 13;11(1):1397. doi: 10.1038/s41467-020-15230-y.
Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a Grp-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal Grp neurons does not affect itch nor pain transmission, demonstrating that spinal Grp neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.
胃泌素释放肽 (GRP) 作为非组胺能瘙痒的神经递质发挥作用，但它的作用部位（感觉神经元与脊髓）仍存在争议。为了确定 GRP 在感觉神经元中的作用，我们构建了一个 floxed Grp 小鼠品系。我们发现，感觉神经元中 Grp 的条件性敲除导致非组胺能瘙痒减弱，而不影响组胺诱导的瘙痒。利用 Grp-Cre 敲入小鼠品系，我们表明皮肤的上表皮仅被 GRP 纤维支配，其通过皮肤中的光遗传学和化学遗传学激活会引起瘙痒而非疼痛相关的抓挠或擦拭行为。相比之下，脊髓 Grp 神经元的交叉遗传消融不会影响瘙痒或疼痛传递，表明脊髓 Grp 神经元对于瘙痒传递不是必需的。这些数据表明，GRP 是感觉神经元中用于非组胺能瘙痒的神经肽，而 GRP 感觉神经元专门用于传递瘙痒。
