miR-143 Regulated Inflammatory Pain by Target Rab1a in Spinal Dorsal Horn

Inflammation induces changes in nociceptive neurons which contribute to both peripheral and central sensitization of pain-sensitive pathways. Plastic changes in sensory neuron excitability are considered the cellular basis of persistent pain. It is well investigated that microRNA can modulate gene expression impact on pain. It has reported miR-143 was downregulated in dorsal root ganglion (DRG) in inflammatory mice. However, less information is available about contribution of miRNA in pain behavior. Here, we demonstrate that miR-143 is also downregulated in spinal dorsal horn. Local increase of miR-143 by using an miR-143 mimic can suppress established inflammatory pain. Furthermore, block miR-143 function was sufficient to cause pain-related behaviors in intact mice. miR-143 targeted the Rab1a gene, and decreased miR-143 associated with pain caused increased Rab1a protein expression, independent of messenger RNA levels. Consistently, miR-143 overexpression in spinal cord suppressed increased Rab1a expression and normalized long-lasting hyperexcitability of nociceptive neurons. These findings demonstrate miR-143 downregulation is causally involved in maintenance of inflammatory pain through regulation of Rab1a and miR-143 supplement offers a novel therapeutic strategy specific for chronic inflammatory pain.