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Qianliang Wang,1,* Hongzhen Ai,1,* Jinglin Liu,1,* Min Xu,2 Zhuang Zhou,1 Chen Qian,1 Ye Xie,1 Jun Yan1 1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; 2Department of Orthopedics, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China *These authors contributed equally to this work Background: Radicular pain, caused by a lesion or autologous nucleus pulposus (NP) implantation, is associated with alteration in gene expression of the pain-signaling pathways. lncRNAs have been shown to play critical roles in neuropathic pain. However, the mechanistic function of lncRNAs in lumbar disc herniation (LDH) remains largely unknown. Identifying different lncRNA expression under sham and NP-implantation conditions in the spinal cord is important for understanding the molecular mechanisms of radicular pain.Methods: LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. The mRNA and lncRNA microarray analyses demonstrated that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly altered at 7 days post operation. The expression patterns of several mRNAs and lncRNAs were further proved by qPCR.Results: LDH produced persistent mechanical and thermal hyperalgesia. A total of 19 lncRNAs was differentially expressed (>1.5-folds), of which 13 was upregulated and 6 was downregulated. In addition, a total of 103 mRNAs was markedly altered (>1.5-folds), of which 40 was upregulated and 63 downregulated. Biological analyses of these mRNAs further demonstrated that the most significantly upregulated genes in LDH included chemotaxis, immune response, and positive regulation of inflammatory responses, which might be important mechanisms underlying radicular neuropathic pain. These 19 differentially expressed lncRNAs have overlapping mRNAs in the genome, which are related to glutamatergic synapse, cytokine-cytokine receptor interaction, and the oxytocin-signalling pathway.Conclusion: Our findings revealed the alteration of expression patterns of mRNAs and lncRNAs in the spinal cord of rats in a radicular pain model of LDH. These mRNAs and lncRNAs might be potential therapeutic targets for the treatment of radicular pain. Keywords: lumbar disc herniation, spinal cord, radicular pain, lncRNA

Mitochondria are multifaceted organelles that serve to power critical cellular functions, including act as power generators of the cell, buffer cytosolic calcium overload, production of reactive oxygen species, and modulating cell survival. The structure and the cellular location of mitochondria are critical for their function and depend on highly regulated activities such as mitochondrial quality control (MQC) mechanisms. The MQC is regulated by several sets of processes: mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy, and other mitochondrial proteostasis mechanisms such as mitochondrial unfolded protein response (mtUPR) or mitochondrial-derived vesicles (MDVs). These processes are important for the maintenance of mitochondrial homeostasis, and alterations in the mitochondrial function and signaling are known to contribute to the dysregulation of cell death pathways. Recent studies have uncovered regulatory mechanisms that control the activity of the key components for mitophagy. In this review, we discuss how mitophagy is controlled and how mitophagy impinges on health and disease through regulating cell death.