Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice

Abstract

Chen Tu, 1 Di-Zheng Wu, 1 Yu-Sheng Huang, 1 Jing-Shen Zhuang, 1 Ji-Huan Zeng, 2 Ping Xu, 1 Ting-Ting Meng, 3 Zhao-Ming Zhong 1 1Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Orthopaedic Surgery, Jiangxi Province People’s Hospital, Nanchang University, Nanchang, People’s Republic of China; 3Department of Anaesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhao-Ming Zhong; Ting-Ting MengNanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of ChinaEmail [email protected]; [email protected]: Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain.Methods: Osteoporosis was induced in mice by ovariectomy (OVX). Pain-related behaviours were assessed by measuring sensitivity to mechanical, thermal and cold stimulation. The expression of pain-related transcripts, such acid-sensing ion channel 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP), was evaluated. Plasma markers of oxidative stress were also measured. In addition, the effects of the reactive oxygen species scavenger phenyl N-tert-butylnitrone (PBN) on these parameters were assessed.Results: The OVX mice presented hyperalgesia, as demonstrated by decreased paw withdrawal thresholds to mechanical stimulation and withdrawal latencies to thermal and cold stimulation, along with upregulated expression of ASIC3, TRPV1 and CGRP in the dorsal root ganglia, spinal cord and thalamus tissue. OVX elevated the plasma levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). However, the administration of PBN alleviated these effects.Conclusion: Our results indicated that oxidative stress contributes to hyperalgesia in OVX mice. Enhanced oxidative stress may be associated with osteoporotic pain. Antioxidant treatment could help alleviate chronic pain in postmenopausal osteoporotic patients.Keywords: osteoporosis, hyperalgesia, oxidative stress, PBN

Keywords

• osteoporosis. hyperalgesia. oxidative stress. pbn.