Abolition of the miRNA pathway in the Nav1.8 population of nociceptive neurons attenuated inflammatory pain. We postulated that altered miRNA levels after peripheral nerve Dasatinib 302962-49-8 injury can contribute to growth programs that promote axonal regeneration. Here we show that an axotomyregulated miRNA, miR-21, promotes neurite growth from injured adult DRG neurons by targeting the Sprouty2 protein. Our results uncover a role for miRNAs in regulating axonal regeneration following peripheral nerve injury. Sciatic nerve injury activates transcription factors such as c-Jun, ATF3 and Stat3, which in turn modulate gene expression and stimulate axon growth to reconnect with peripheral targets. Here we investigated if sciatic nerve injury induced changes in small noncoding RNAs that can regulate gene expression at the post-transcriptional level. Using a microarray screen we identified 8 miRNAs that were regulated after axotomy. We further show that miR-21 enhanced neurite outgrowth in adult rat DRG neurons. This, to our knowledge, is the first time a regenerative role for miR-21 in neurons has been demonstrated. Of the 8 miRNAs that were regulated after axotomy, only miR431 and miR-138 have been shown to be expressed in the central nervous system. miR-223 appears to be predominantly present in hematopoietic cells but interestingly has been shown to be highly expressed in neutrophils that are present in the spinal cord during the early phase of spinal cord injury. miR-431 was found to be present in embryonic and postnatal mouse brains but levels were lower in adult mouse brains. miR-383 is expressed in germ cells and has been shown to target interferon regulatoryfactor 1, a transcription factor that controls expression of genes related to inflammation and injury. IRF-1 expression is increased in neurons following ischaemic injury and it is plausible that decreased miR-383 in the DRG following axotomy can modulate signalling cascades through IRF-1. miR-138 is interesting as it is highly enriched in the synapse and negatively regulates dendritic spine size by targeting the depalmitoylation enzyme acyl protein thioesterase 1. Interestingly in the same paper, miR-21 also exhibited significant increased expression in rat synaptosomes compared to whole forebrain extract. miR-21 is a commonly dysregulated miRNA in many forms of cancer and cardiovascular disease however its function in the nervous system has not been examined. We showed that miR-21 was significantly increased in the DRG 2 days after axotomy, and that this increase was sustained up to 28 days post-injury.