microRNA-30c as a biomarker and potential target in neuropathic pain states

M Tramullas1,2, S Velategui1,2, R García1,2, A Lantero1,2, R Santillán3, AV Villar1,2, MA Hurlé1,2. 1Faculty of Medicine, University of Cantabria, Phisiology & Pharmacology Deparment,, Spain, 2Education and Research Institute Marqu é s de Valdecilla, IFIMAV, Spain, 3Hospital Marqu é s de Valdecilla, Clinical Pharmacology, Spain

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. microRNAs (miRNAs) are small, noncoding RNAs that direct the post-transcriptional suppression of gene expression. Recent evidence suggests that miRNAs play a regulatory role in several pathological pain states. The goals of this study were to assess in a rat model of peripheral neuropathy whether the expression levels of mir-30c in the cerebrospinal fluid (CSF), plasma and pain related CNS structures are regulated following nerve injury and their relationship with pain intensity.

The experiments were carried out in male rats (250 g) housed in a room kept under standard controlled conditions (21 ± 1°C, 55 ± 10% humidity), on a 12 h light/dark cycle (lights on at 08:00 am). Neuropathic pain was induced using the spared nerve injury (SNI) model. Under isofluorane anaesthesia, the tibial and common peroneal branches of the sciatic nerve were sectioned, leaving the sural branch intact. Neuropathic pain-related behaviours (mechanical allodynia) were assessed by using Von Frey monofilaments every two days after SNI. CSF and plasma samples were collected from each animal under basal conditions and 10 days after sciatic nerve injury, when maximal hyperalgesia was evident. Samples from the dorsal horn of the spinal cord and the periacueductal gray matter were obtained from rats sham operated or subjected to SNI 10 days after the surgery, at the end of the behavioural study. When compared with sham rats, SNI rats displayed a significant reduction in pain threshold (p<0.01). The animals subjected to SNI showed a significant increase of miR-30c levels in the CSF (baseline: 2.1 ± 0.9 vs SNI 8.4 ± 1.3; p<0.01) and plasma (baseline: 1.2 ± 0.3 vs SNI 5.6 ± 1.3; p<0.01). Pearson´s correlation analysis indicated that there was a positive correlation between the expression levels of mir-30c in CSF and plasma (p<0.05). Furthermore, the nociceptive thresholds inversely correlated with the fold increase of miR-30c levels in both CSF and plasma (p<0.05).

Our data indicate that miR-30c might serve as a biomarker of neuropathic pain states and suggest the potential for miR-30c to play a direct role in the maladaptive plasticity of the CNS underlying neuropathic pain.Supported by RTICS (RD06/001/1016) and SAF2010/16894.