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

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

doi:10.3389/fnagi.2021.654761

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.

Highlights

Pruritus is an increasingly concerning clinical problem, which frequently occurs in older people and causes needless suffering of patients’ lives
We first demonstrated that aging down-regulated Neuropeptide Y (NPY) in the spinal dorsal horn, that NPY deficiency evoked mechanical itch in young mice and intensified alloknesis in aged mice, and that pharmacological activation of the NPY/neuropeptide Y receptor 1 (NPY1R) signaling alleviated alloknesis in aged mice
Accumulating studies had suggested that the NPY system, especially in the brain, was linked to the aging process and lifespan determination (Hua et al, 1991; Peng et al, 1993; Michalkiewicz et al, 2003; Gehrig et al, 2012)

Summary

Introduction

Pruritus is an increasingly concerning clinical problem, which frequently occurs in older people and causes needless suffering of patients’ lives. Senile pruritus is defined as chronic pruritus, which lasts 6 or more weeks in a person over 65 years old with elusive causes determined by appropriate examination (Ward and Bernhard, 2005; Valdes-Rodriguez et al, 2015). Previous studies showed a wide prevalence of senile pruritus, almost one-third in a nursing home in America. Increasing along with age, senile pruritus might be a part of the aging process (Chang et al, 2013; Clerc and Misery, 2017).

Methods

Results

Conclusion