Neuropathic pain develops after injury of the somatosensory system [1, 2]. It is characterized by spontaneous continuous or paroxysmal pain and stimuli-evoked pain [1, 3]. It has been emerged as one of the most difficult pain syndromes, affecting 7–10% of the population [1]. Moreover, the incidence of neuropathic pain is increasing with the aging of the global population [1]. Despite recent improvements, the management of neuropathic pain remains unsatisfactory, mainly due to insufficient understanding of the molecular mechanisms underlying the syndrome [2, 4]. Therefore, there is a need to reveal the underlying mechanisms to benefit the clinical management of neuropathic pain.
Dorsal root ganglion (DRG) contains a great proportion of body's sensory neurons, which are critical for transducing sensory information from the periphery to the central nervous system [5, 6]. Accumulating evidence has highlighted that the development of neuropathic pain is associated with changes in DRG neurons, such as release of cytokines and dysregulation of ion channels[5]. In addition to changes in the expression of individual genes, recent studies have highlighted gene expression alterations in DRG of neuropathic pain. After examining gene expression in DRG of normal rats and peripheral axotomy operated rats, Xiao et al., identified significant differences in the expression of 173 genes, including neuropeptides, ion channels and synaptic vesicle proteins [10]. Reinhold et al., have confirmed differential expression patterns between damaged DRG neurons and adjacent neurons, using fluorescent neuronal tracers [11]. Furthermore, universal alterations of miRNA expression in DRG have been demonstrated in neuropathic pain. Li et al., have identified a total of 114 differentially expressed miRNAs in DRG of neuropathic pain rats[12]. Besides, in another study, the expression of a total of 42 miRNAs was shown to be significantly altered in DRG of streptozotocin (STZ)-induced diabetic neuropathic pain mice [13].
Circular RNAs (circRNAs) are a large family of covalently closed RNA molecules with regulatory roles in gene transcription, miRNA function and protein production [14–16]. CircRNAs are expressed in diverse cell types and preferentially expressed in neural tissues [16]. The expression levels of circRNAs are dynamically modulated in neurons, which are essential for synaptic plasticity and neuronal function [17]. Alterations in the expression of circRNAs may play roles in neuropathic pain[18]. In a recent study, 469 circRNAs were identified to be differentially expressed in spinal dorsal horn of CCI rats [18]. However, our knowledge about the alterations in the expression of circRNAs in DRG of neuropathic pain is limited.
In order to gain a global view of aberrant circRNA expression in DRG of CCI rats, we established CCI model and evaluated circRNA expression levels in DRG using next generation sequencing technology. Differentially expressed circRNAs (DEcircRNAs) between CCI and NC rats were identified and subsequently validated by quantitative real-time PCR (qPCR). Functional annotation was implemented to explore the biological function of DEcircRNAs.