Research ArticlePain

MicroRNA-30c-5p modulates neuropathic pain in rodents

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Science Translational Medicine  08 Aug 2018:
Vol. 10, Issue 453, eaao6299
DOI: 10.1126/scitranslmed.aao6299

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Targeting a microRNA for neuropathic pain

Neuropathic pain is a debilitating condition resulting from nerve damage. Often, patients do not achieve pain relief with currently available therapies. A better understanding of the mechanisms mediating neuropathic pain could help to identify more effective therapies. Now, Tramullas et al. show that neuropathic pain in rodents was associated with increased expression of the microRNA miR-30c-5p in the brain, cerebrospinal fluid, and plasma. In addition, miR-30c-5p was up-regulated in plasma and cerebrospinal fluid from patients with peripheral ischemia–induced pain. Inhibiting this microRNA in the rodent model produced analgesic effects. The results suggest that targeting miR-30c-5p might be an effective strategy for treating neuropathic pain.

Abstract

Neuropathic pain is a debilitating chronic syndrome that is often refractory to currently available analgesics. Aberrant expression of several microRNAs (miRNAs) in nociception-related neural structures is associated with neuropathic pain in rodent models. We have exploited the antiallodynic phenotype of mice lacking the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transforming growth factor–β (TGF-β) pseudoreceptor. We used these mice to identify new miRNAs that might be useful for diagnosing, treating, or predicting neuropathic pain. We show that, after sciatic nerve injury in rats, miR-30c-5p was up-regulated in the spinal cord, dorsal root ganglia, cerebrospinal fluid (CSF) and plasma and that the expression of miR-30c-5p positively correlated with the severity of allodynia. The administration of a miR-30c-5p inhibitor into the cisterna magna of the brain delayed neuropathic pain development and reversed fully established allodynia in rodents. The mechanism was mediated by TGF-β and involved the endogenous opioid system. In patients with neuropathic pain associated with leg ischemia, the expression of miR-30c-5p was increased in plasma and CSF compared to control patients without pain. Logistic regression analysis in our cohort of patients showed that the expression of miR-30c-5p in plasma and CSF, in combination with other clinical variables, might be useful to help to predict neuropathic pain occurrence in patients with chronic peripheral ischemia.

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