Spinal RAMP1-mediated neuropathic pain sensitisation in the aged mice through the modulation of CGRP-CRLR pain signalling
Yi Qin,
Xuemei Chen,
Zhangjie Yu,
Xiaoxin Zhou,
Yihao Wang,
Qi Li,
Wanbing Dai,
Yizhe Zhang,
Sa Wang,
Yinghui Fan,
Jie Xiao,
Diansan Su,
Yingfu Jiao,
Weifeng Yu
Affiliations
Yi Qin
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China
Xuemei Chen
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China
Zhangjie Yu
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China
Xiaoxin Zhou
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Yihao Wang
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Qi Li
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Wanbing Dai
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Yizhe Zhang
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Sa Wang
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Yinghui Fan
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Jie Xiao
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China
Diansan Su
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China; Corresponding author. Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China.
Yingfu Jiao
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China; Corresponding author. Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China.
Weifeng Yu
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, China; Corresponding author. Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China.
Pain sensitivity varies depending on both the state and age of an individual. For example, chronic pain is more common in older individuals, but the underlying mechanisms remain unknown. This study revealed that 18-month-old mice (aged) experienced more severe and long-lasting allodynia and hyperalgesia in the chronic constriction injury (CCI)-induced pain state compared to 2-month-old mice. Interestingly, the aged mice had a higher baseline mechanical pain threshold than the adult mice. The expression of spinal receptor-active modification protein 1 (RAMP1), as a key component and regulator of the calcitonin gene-related peptide (CGRP) receptor for nociceptive transmission from the periphery to the spinal cord, was reduced in the physiological state but significantly increased after CCI in the aged mice compared to the adult mice. Moreover, when RAMP1 was knocked down using shRNA, the pain sensitivity of adult mice decreased significantly, and CCI-induced allodynia in aged mice was reduced. These findings suggest that spinal RAMP1 is involved in regulating pain sensitivity in a state- and age-dependent manner. Additionally, interfering with RAMP1 could be a promising strategy for alleviating chronic pain in older individuals.
