Regulation by noncoding RNAs of local translation, injury responses, and pain in the peripheral nervous system

• Published in: Neurobiology of pain 2023-01, Vol.13, p.100119, Article 100119
• Main Authors: Li, Xinbei, Jin, Daniel S., Eadara, Sreenivas, Caterina, Michael J., Meffert, Mollie K.
• Format: Article
• Language: English
• Subjects: Local translation; ncRNAs; Nerve injury; Neuropathic pain; Original; Peripheral nerve; Plasticity
• ISSN: 2452-073X; 2452-073X
• DOI: 10.1016/j.ynpai.2023.100119

•Neuropathic pain results from maladaptive plasticity within nociceptive pathways.•Altered mRNA translation contributes to the enduring pathophysiological changes supporting nociceptive plasticity and persistent pain.•Noncoding RNAs (ncRNAs) play essential roles in post-transcriptional regulation of local proteomes in peripheral tissue following injury.•ncRNAs that are dysregulated in peripheral tissue following injury could contribute to nociceptive plasticity and the generation of neuropathic pain. Neuropathic pain is a chronic condition arising from damage to somatosensory pathways that results in pathological hypersensitivity. Persistent pain can be viewed as a consequence of maladaptive plasticity which, like most enduring forms of cellular plasticity, requires altered expression of specific gene programs. Control of gene expression at the level of protein synthesis is broadly utilized to directly modulate changes in activity and responsiveness in nociceptive pathways and provides an effective mechanism for compartmentalized regulation of the proteome in peripheral nerves through local translation. Levels of noncoding RNAs (ncRNAs) are commonly impacted by peripheral nerve injury leading to persistent pain. NcRNAs exert spatiotemporal regulation of local proteomes and affect signaling cascades supporting altered sensory responses that contribute to hyperalgesia. This review discusses ncRNAs found in the peripheral nervous system (PNS) that are dysregulated following nerve injury and the current understanding of their roles in pathophysiological pain-related responses including neuroimmune interactions, neuronal survival and axon regeneration, Schwann cell dedifferentiation and proliferation, intercellular communication, and the generation of ectopic action potentials in primary afferents. We review progress in the field beyond cataloging, with a focus on the relevant target transcripts and mechanisms underlying pain modulation by ncRNAs.