Abstract

Linking Pain-Regulated Exosomal-miRNAs to Target Expression in the Brain

natasha sosanya, Staff Scientist, USAISR

Recently, our lab identified a number of differentially expressed (DE) circulating exosomal miRNAs (ex-miRNAs) in rats following spinal nerve ligation (SNL). The objective of this current study is to determine whether the targets of DE, circulating ex-miRNAs demonstrate differential expression in specific brain regions following nerve injury. Male Sprague-Dawley rats underwent either SNL or sham surgery on the right L5 nerve, while anesthetized. Prior to injury and on days 3 and 15 post-nerve injury, mechanical allodynia was assessed and plasma was collected. DE ex-miRNAs were identified by small RNA sequencing. Brains were harvested from all rats and micro dissected. Expression of several ex-miRNA targets in the contralateral and ipsilateral dorsal prefrontal cortex (PFC) was determined. p-VEGFR2 and p-P70S6K was increased in the contralateral PFC and p-ERK1 and p-P70S6K was elevated in the ipsilateral PFC of injured rats. This mirrors our previous findings showing a downregulation of the circulating ex-miRNAs modulating these pathways. Overall, ex-miRNAs are key regulators, biomarkers, and targets in the treatment of neuropathic pain. Further work is ongoing to examine target expression of a wider range of DE ex-miRNAs in multiple brain regions.