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

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.

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial

“…Given the absence of effective preventive agents, clinicians should carefully assess the benefits of agents known to cause CIPN against the risks of developing long-term irreversible neuropathy, especially among patients with underlying neuropathy and with conditions that predispose to neuropathy (e.g., diabetes mellitus and/or a personal or family history of hereditary neuropathies). Clinical studies have described that miR-30c-5p levels are related with neuropathic pain intensity [ 72 ]. This study opens the possibility in the future of using micro-RNA as a clinical marker of this syndrome.…”

“…Experimental studies inducing damage in the sciatic nerve described an increase in miRNA (specifically miR-30c-5p) in cerebrospinal fluid and plasma. This miRNA can decrease the expression of TGF-β1 and be associated with neuropathic symptoms [ 72 ]. Indeed, the inhibition of miR-30c-5p increased TGF-β1 and decreased neuropathic pain and suggests the therapeutic potential of this approach [ 72 ].…”

“…This miRNA can decrease the expression of TGF-β1 and be associated with neuropathic symptoms [ 72 ]. Indeed, the inhibition of miR-30c-5p increased TGF-β1 and decreased neuropathic pain and suggests the therapeutic potential of this approach [ 72 ]. Thus, the modulation of TGF-β1 by ozone therapy could be another of the action mechanisms of ozone.…”

MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells

“…MiR-30c prevented diabetic cardiomyopathy by reducing the peroxisome proliferator-activated receptor alpha level [30]. Moreover, miR-30c-5p regulated neuropathic pain of rodents and was highly expressed in the spinal cord and dorsal root ganglia [31]. Furthermore, miR-30c-5p was associated with macrophage-mediated inflammation and pro-atherosclerosis signal pathways [32].…”

Developing Modern Pain Therapies

“…Another recent development is the targeting of novel miRNA pathways; there is growing evidence for the involvement of miRNAs in both the maintenance and in initiation of chronic pain. Synthesized single strand inhibitors of these miRNAs have recently shown prolonged efficacy of weeks (Tramullas et al, 2018). An advantage of these methodologies is they show long lasting relief and, in some cases, may provide local relief targeting pain specific pathways or using drugs unable to cross the blood-brain barrier.…”