Differential Expression of MicroRNAs in Mouse Pain Models

Abstract

BackgroundMicroRNAs (miRNAs) are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs. The expression of numerous brain-specific miRNAs with a high degree of temporal and spatial specificity suggests that miRNAs play an important role in gene regulation in health and disease. Here we investigate the time course gene expression profile of miR-1, -16, and -206 in mouse dorsal root ganglion (DRG), and spinal cord dorsal horn under inflammatory and neuropathic pain conditions as well as following acute noxious stimulation.ResultsQuantitative real-time polymerase chain reaction analyses showed that the mature form of miR-1, -16 and -206, is expressed in DRG and the dorsal horn of the spinal cord. Moreover, CFA-induced inflammation significantly reduced miRs-1 and -16 expression in DRG whereas miR-206 was downregulated in a time dependent manner. Conversely, in the spinal dorsal horn all three miRNAs monitored were upregulated. After sciatic nerve partial ligation, miR-1 and -206 were downregulated in DRG with no change in the spinal dorsal horn. On the other hand, axotomy increases the relative expression of miR-1, -16, and 206 in a time-dependent fashion while in the dorsal horn there was a significant downregulation of miR-1. Acute noxious stimulation with capsaicin also increased the expression of miR-1 and -16 in DRG cells but, on the other hand, in the spinal dorsal horn only a high dose of capsaicin was able to downregulate miR-206 expression.ConclusionsOur results indicate that miRNAs may participate in the regulatory mechanisms of genes associated with the pathophysiology of chronic pain as well as the nociceptive processing following acute noxious stimulation. We found substantial evidence that miRNAs are differentially regulated in DRG and the dorsal horn of the spinal cord under different pain states. Therefore, miRNA expression in the nociceptive system shows not only temporal and spatial specificity but is also stimulus-dependent.

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

“…These changes appear to be the result of the specific regulation of miRNAs in individual tissues or organs along the pain transmission pathway, rather than a global change in miRNA or small RNA levels, as the miRNA changes observed after the induction of bCCI were unique to their specific region. Previous studies have determined that miRNA expression in the nociceptive system is not only temporally and spatially specific, but also stimulus-dependent (14,22). However, to our knowledge, little is known about the differential expression of miRNAs in the nociceptive pathway during bCCI, and our is the first study to investigate this.…”

“…Furthermore, changes (either increases or decreases) in miRNA expression have been found in many disease states (22)(23)(24). Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve.…”

Soluble Intercellular Adhesion Molecule-1: A Potential Biomarker for Pain Intensity in Chronic Pain Patients

“…In mouse, Kusuda et al found that miRNAs are differentially expressed in the spinal cord under different pain conditions [33]. In CLBP patients, a recent work reported the predictive implication for therapy response for miRNA hsa-miR-124 [34].…”

Role of MicroRNA in Visceral Pain

“…This finding strongly suggests the involvement of miRNAs in long-term cortical plasticity following esophageal acid exposure early in life. Here, we review specific miRNAs that have been identified as the regulators of nociceptive activity and highlight their possible association with pain processing in various pain conditions (Table 87, 99,100,101,103,[105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122] ).…”