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Sci Transl Med. 2018 Aug 8;10(453). pii: eaao6299. doi: 10.1126/scitranslmed.aao6299.

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

Author information

1
Departamento de Fisiología y Farmacología, Universidad de Cantabria, E-39011 Santander, Spain.
2
Instituto de Investigación Valdecilla, E-39011 Santander, Spain.
3
Servicio de Anestesiología, Hospital Universitario Valdecilla, E-39008 Santander, Spain.
4
Departamento de Ciencias Médicas y Quirúrgicas, Universidad de Cantabria, E-39011 Santander, Spain.
5
CIBER de Epidemiología y Salud Pública, Spain.
6
Departamento de Fisiología y Farmacología, Universidad de Cantabria, E-39011 Santander, Spain. hurlem@unican.es.

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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