MicroRNA-30c-5p modulates neuropathic pain in rodents
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 phenoty...
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Published in | Science translational medicine Vol. 10; no. 453 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
08.08.2018
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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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AbstractList | 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. |
Author | Velategui, Sara Tramullas, Mónica García, Raquel de la Fuente, Roberto Carcelén, María Francés, Raquel Llorca, Javier Hurlé, María A |
Author_xml | – sequence: 1 givenname: Mónica orcidid: 0000-0002-2447-8928 surname: Tramullas fullname: Tramullas, Mónica organization: Instituto de Investigación Valdecilla, E-39011 Santander, Spain – sequence: 2 givenname: Raquel orcidid: 0000-0003-1428-4852 surname: Francés fullname: Francés, Raquel organization: Instituto de Investigación Valdecilla, E-39011 Santander, Spain – sequence: 3 givenname: Roberto surname: de la Fuente fullname: de la Fuente, Roberto organization: Servicio de Anestesiología, Hospital Universitario Valdecilla, E-39008 Santander, Spain – sequence: 4 givenname: Sara surname: Velategui fullname: Velategui, Sara organization: Departamento de Fisiología y Farmacología, Universidad de Cantabria, E-39011 Santander, Spain – sequence: 5 givenname: María orcidid: 0000-0002-0233-2688 surname: Carcelén fullname: Carcelén, María organization: Instituto de Investigación Valdecilla, E-39011 Santander, Spain – sequence: 6 givenname: Raquel surname: García fullname: García, Raquel organization: Instituto de Investigación Valdecilla, E-39011 Santander, Spain – sequence: 7 givenname: Javier orcidid: 0000-0001-8569-861X surname: Llorca fullname: Llorca, Javier organization: CIBER de Epidemiología y Salud Pública, Spain – sequence: 8 givenname: María A orcidid: 0000-0002-7710-1358 surname: Hurlé fullname: Hurlé, María A email: hurlem@unican.es organization: Instituto de Investigación Valdecilla, E-39011 Santander, Spain |
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