Downregulation of Selective microRNAs in Trigeminal Ganglion Neurons Following Inflammatory Muscle Pain

Abstract

Active regulation of gene expression in the nervous system plays an important role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA) negatively regulates gene expression via posttranscriptional or transcriptional inhibition of specific genes. To explore the possible involvement of miRNA in gene regulation during inflammatory pain, we injected complete Freund's adjuvant (CFA) unilaterally into the rat masseter muscle and quantified changes in neuron-specific mature miRNAs in the trigeminal ganglion (TG). Real-time reverse-transcription polymerase chain reaction revealed significant, but differential, downregulation of mature miR-10a, -29a, -98, -99a, -124a, -134, and -183 in the ipsilateral mandibular division (V3) of the TG within 4 hr after CFA. In contrast, levels of tested miRNAs did not change significantly in the contralateral V3 or the ipsilateral ophthalmic and maxillary divisions of the TG from inflamed rats, nor in the ipsilateral V3 of saline-injected animals. The downregulated miRNAs recovered differentially to a level equal to or higher than that in naive animals. Full recovery time varied with miRNA species but was at least 4 days. Expression and downregulation of some miRNAs were further confirmed by in situ hybridization of TG neurons that innervate the inflamed muscle. Although neurons of all sizes expressed these miRNAs, their signals varied between neurons. Our results indicate that miRNA species specific to neurons are quickly regulated following inflammatory muscle pain.

Circulating microRNA expression profile: a novel potential predictor for chronic nervous lesions

“…3 from the neuropathic pain study, were compared with previous reports in rodent models for pain investigation. This study is the first report about the association between miRNAs and neuropathic pain in SNL rats, although there was some overlap with previous studies, which focused on the expression changes of miRNAs [27,29,42,44,49].…”

“…Target prediction algorithms use different parameters to provide candidate target genes for miRNAs. Some of the miRNAs are of special interest concerning their putative targets, so TargetScan was used to identify putative targets and to provide a foundation for functional analyses of neuropathic pain as done in previous reports [42][43][44].…”

Role of MicroRNA in Visceral Pain

“…86 In an inflammatory rat model of CFA-induced muscle pain, several miRNAs including miRs-10a, -29a, -98, -99a, -124a, -134, and -183 were significantly downregulated in neurons of the ipsilateral trigeminal ganglion. 87 This downregulation of specific miRNAs was considered to increase the expression of several "pain-related" proteins and therefore, facilitated the development of inflammation and allodynia. On the other hand, upregulation of miR-155 and miR-223 in the prefrontal cortex has been reported following carrageenan-induced facial inflammation in mice.…”

miRNAs being Key Contributors to Chronic Pain Development and Maintenance

“…Earlier studies have shown that peripheral inflammation and nerve injury initiate changes in the expression of some miRNAs and Kcna2 AS RNA in DRG [10][11][12][13] and these changes might be responsible for inflammation/nerve injury-induced alterations of some painassociated genes, an increase in DRG neuronal excitability, and pain hypersensitivity [11,13]. Recent evidence indicates that ncRNAs might be the pivotal player in the mechanisms that underlie the development and maintenance of chronic pain.…”

“…For instance, in an inflammatory rat model of CFA-induced muscle pain, the authors suggested that this decrease in miRNAs allows for an upregulation of ""pain-related"" proteins that facilitated the development of inflammation and allodynia. [10] …”