MiR-203 Involves in Neuropathic Pain Development and Represses Rap1a Expression in Nerve Growth Factor Differentiated Neuronal PC12 Cells

Abstract

Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…SNL-induced mechanical allodynia significantly correlated with the decreased expression of miR-183 in DRG cells [71]. Replacement of miR-183 downregulates SNL-induced increases in Nav1.3 and BDNF expression and attenuates SNL-induced mechanical allodynia [72] have both reported a 10-fold decrease in miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns.…”

The role of microRNAs in the healing of diabetic ulcers

“…MiR‐203 is associated with apoptosis of beta‐pancreatic cells and inhibits TNF‐α and IL‐24 expression in the skin, and despite increasing differentiation of keratinocytes, it inhibits the migration and proliferation of keratinocytes . MiR‐203 is also associated with neuropathic pain . On the other hand, increasing the expression of miR‐210 due to hypoxia and increased glucose levels silences receptor B1 of Activin A and, similar to miR‐203, increases the differentiation of keratinocytes …”

“…104,105 MiR-203 is also associated with neuropathic pain. 150,151 On the other hand, increasing the expression of miR-210 due to hypoxia and increased glucose levels 99 silences receptor B1 of Activin A 152 and, similar to miR-203, increases the differentiation of keratinocytes. 149…”

Epigenetic regulation of persistent pain

“…Since then, expression of miRNAs in tissues processing pain under various persistent pain conditions has been scrutinized by many laboratories. In most cases miRNA downregulation was found from body fluids including CSF of female patients with fibromyalgia [215] and blood or serum of patients with complex regional pain syndrome [216] and osteoarthritis of the knee and hip joints [217], and tissues of DRG/TG [214, 218–225, 244], the spinal cord [220, 224, 226–227], brain regions [228] and keratinocytes [229] in the early stage of persistent pain [214] or at the later stage [218, 228]. Smaller numbers of miRNAs were found to be upregulated in the circulation of complex regional pain syndrome [216] and IBS patients [230], DRG [221, 231, 244], and the spinal cord [219, 232] under various persistent pain conditions.…”

“…Smaller numbers of miRNAs were found to be upregulated in the circulation of complex regional pain syndrome [216] and IBS patients [230], DRG [221, 231, 244], and the spinal cord [219, 232] under various persistent pain conditions. Abnormal expression profile of miRNAs was found in DRG of bone cancer pain [233] and osteoarthritis rats [224], the spinal cord of CCI rats [226, 234] and osteoarthritis rats [224], hippocampi in CFA and CCI rats [235], CSF of females with fibromyalgia [215], or compared with that of mRNAs in hippocampus after CCI [236]. Using in situ hybridization, a number of laboratories have identified neuronal miRNAs in DRG or in the spinal cord [218, 222–223, 225, 231, 237] and glial miRNAs in the spinal cord [227, 232].…”