Neuropeptides are associated with pain threshold and bone microstructure in ovariectomized rats

Abstract Objectives Postmenopausal osteoporosis (PMO) is a metabolic skeletal disorder with impaired bone density and bone quality in postmenopausal women. The aim of the present study was to investigate the correlation between neuropeptides, bone microstructure and pain threshold in ovariectomized (OVX) rats. Methods Female rats were randomly divided into the ovariectomized (OVX) group and the sham surgery (SHAM) group. Bone microstructure and immunocytochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in tibial and DRG were performed. Pain threshold was assessed at post-operative 11 weeks. Pearson correlation coefficients were calculated between neuropeptides, bone microstructure and pain threshold. Results Significant decreases in bone volume fraction (BV/TV) and trabecular number (Tb. N) but significant increases in trabecular spacing (Tb.Sp) were showed in OVX group. Mechanical pain threshold (MPT) in OVX group was significantly decreased. The MOD values for SP, CGRP and VIP of tibial in OVX group were significantly lower, whereas NPY, NPY1R and NPY2R were significantly higher. And SP, CGRP, VIP, NPY and NPY2R of DRG were significantly increased in OVX group, while NPY1R was significantly decreased. Correlation analysis showed that NPY, Y1R and Y2R in bone were negatively correlated with BV/TV. MPT was negatively correlated with NPY and Y2R in DRG, and positively correlated with Y1R in DRG. Conclusions Our results suggested that SP, CGRP, VIP and NPY were involved in the osteoporotic bone microstructure and mechanical hypersensitivity in OVX rats, indicating the potential to utilize neuropeptides as novel therapeutic targets for PMO.