Simple aches pains send us scrambling for the ibuprofen, so we can only imagine how hard it is to deal with chronic pain. Following up on the role that microRNAs play in some neurological processes, researchers found that miR-103 regulates certain pain channels, and may one day be the a key to chronic pain relief.
For some people, chronic pain stems from an injury that never stopped hurting; for others, there’s no obvious trigger for the pain—but either way, it’s there, and it won’t go away. Researchers in France studied a particular calcium channel, Cav1.2-LTC, which is known to be involved with hypersensitivity to pain, and is made up of three protein subunits in order to determine if it might be controlled by miRNAs.
Bioinformatics analyses suggested that miR-103 could bind to and inhibit all of the Cav1.2-LTC subunits, and in in vitro experiments, miR-103 prevented their expression from reporter plasmids, whereas miR-103 with a mutated or deleted seed region didn’t. Stopping miR-103 activity with an inhibitor (miR-103-KD) increased endogenous subunit expression in cells. The researchers also saw the same kind of thing with imaging experiments and termed this up- and down-regulation “bidirectional.”
Next, the French team went in vivo. Rats injected with miR-103-KD became hypersensitive to pain. In a rat model of pain (rats with spinal nerve ligation; SNL), the mRNA levels for all three subunits were very high, while miR-103 levels were low. Injecting SNL rats with miR-103 reduced subunit expression and restored the animals to near-normal levels of pain tolerance.
The researchers think that miR-103 is a potential therapeutic target for the treatment of chronic pain. Get all the pain relieving details at EMBO Journal, July 2011.