MicroRNA-30c-5p modulates neuropathic pain in rodents.
Mónica TramullasRaquel FrancésRoberto de la FuenteSara VelateguiMaría CarcelénRaquel GarcíaJavier LlorcaMaría A HurléPublished in: Science translational medicine (2019)
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.
Keyphrases
- neuropathic pain
- spinal cord
- long non coding rna
- spinal cord injury
- poor prognosis
- cell proliferation
- transforming growth factor
- end stage renal disease
- long noncoding rna
- cerebrospinal fluid
- ejection fraction
- newly diagnosed
- epithelial mesenchymal transition
- peritoneal dialysis
- chronic pain
- pain management
- prognostic factors
- binding protein
- type diabetes
- skeletal muscle
- white matter
- mass spectrometry
- metabolic syndrome
- drug induced
- functional connectivity
- wild type
- postoperative pain