microRNAs (miRNAs) are small, non-coding RNAs involved in all processes in health and disease, including neuropathic pain and neuroregeneration. Upon peripheral nerve injury (PNI), dorsal root ganglia (DRG) neurons exhibit increased excitability and altered signaling, leading to dysregulation of their transcriptomic profiles indicative of neuropathic pain and axono-regenerative processes. The complexity of these neuronal responses makes distinguishing between the mechanisms involved in neuroregeneration and neuropathy highly challenging. To elucidate the role of miRNAs in these processes, we utilized the spared nerve injury (SNI) model and performed paired miRNA:mRNA sequencing on DRG of sham and SNI mice. Subsequently, top dysregulated miRNAs were characterized using a combination of complementary techniques, including bioinformatics, gene and protein expression analyses, behavioral phenotyping, and transgenic mice. In vivo inhibition of miR-21a-5p (top-upregulated) alleviated SNI-induced mechanical hypersensitivity, whereas inhibition and global depletion of the second most upregulated miRNA did not affect injury-induced pain-like behaviors. DRG neurons from miRNA-knockout mice exhibited reduced outgrowth capacity in vitro and overexpression of this miRNA resulted in enhanced neurite outgrowth. Sequencing of sensory neurons derived from transgenic mice revealed deregulated expression of genes involved in neuroregeneration. We propose that after PNI, specific miRNAs act as master regulators of their mRNA-target genes, which are differentially involved in neuronal regeneration and neuropathic pain. By elucidating the complex and diverging cellular responses that are induced after peripheral nerve lesions, our study highlights the importance of dissecting the differential roles of miRNAs and introduces potential novel intervention strategies in the field of neuropathic pain and neuroregeneration.