Lack of Spinal Neuropeptide Y Is Involved in Mechanical Itch in Aged Mice

Huan Cui; Wenliang Su; Yan Cao; Lulu Ma; Guangyan Xu; Wanying Mou; Hanlin Zhang; Jiawen Yu; Chao Ma; Xiuhua Zhang; Yuguang Huang

doi:10.3389/fnagi.2021.654761

Lack of Spinal Neuropeptide Y Is Involved in Mechanical Itch in Aged Mice

Front Aging Neurosci. 2021 May 28:13:654761. doi: 10.3389/fnagi.2021.654761. eCollection 2021.

Authors

Huan Cui¹, Wenliang Su², Yan Cao¹, Lulu Ma², Guangyan Xu², Wanying Mou², Hanlin Zhang¹, Jiawen Yu², Chao Ma^{1

3}, Xiuhua Zhang², Yuguang Huang²

Affiliations

¹ Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
² Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
³ Chinese Institute for Brain Research, Beijing, China.

Abstract

Neuropeptide Y (NPY) signaling plays an essential role in gating the pruritic afferent information in the spinal cord. Recent studies revealed that the aging process down-regulated the expression of NPY in the central nervous system. We propose that the lack of spinal NPY may be involved in certain types of pruritus in the elderly population. This study was designed to investigate the role of NPY in aging-induced itch using the senile mouse model. The expression of NPY in the spinal dorsal horn was compared between young (2 months old) and aged (24 months old) mice. Western blotting and immunohistochemistry showed that the expression of NPY was significantly reduced in the spinal dorsal horn in aged mice. In addition, a neuronal maker of apoptosis, TUNEL, was detected in the NPY positive neurons only in the aged spinal cord. Behavioral assay indicated that light mechanical stimulus evoked significantly more scratching in the aged than in the young mice, whereas chemical-evoked itch and pain-related behaviors were not altered. Intrathecal injection of either NPY or LP-NPY, a NPY receptor 1 (NPY1R) agonist, significantly alleviated the mechanically evoked itch in aged mice without altering the responses to chemical pruritogens. Our study suggested that downregulation of spinal NPY in the aged mice might play a role in the higher incidence of the mechanically evoked itch than that in the young mice. Therapies targeting the NPY system might serve as a potential strategy for alleviating the pruritic symptoms among the elderly population.

Keywords: NPY1R; mechanical itch; neuropeptide Y; senile pruritus; spinal dorsal horn.