Breaking research, published in the journal Science, demonstrates that touch-sensitive nerves switch teams and generate pain in chronic pain conditions. The findings may open the door to better treatments.

neurons firingShare on Pinterest
A new study finds that nerves switch sides to produce chronic nerve pain conditions.

Pain is a difficult but vital area of medical research. It encompasses physiology, neurology, and the murky, subjective world of perception.

Current drugs aimed at treating chronic nerve pain are only partially successful in some people and come with a range of side effects.

The search for more effective medication is ongoing, but because the mechanisms behind chronic nerve pain are not well understood, it is an uphill battle.

For many years, chronic nerve pain was thought to be due to a hypersensitivity in the neurons that transmit pain signals. This view is slowly changing, and recently published work provides an intriguing new angle.

A team of scientists from the Karolinska Institutet in Sweden investigated a group of nerves not traditionally thought to be involved in the sensation of pain.

In conditions involving chronic nerve pain, just the slightest touch can result in intense pain. How this might occur has long been a mystery. It is known that certain sensory neurons only transmit “pleasant tactile” sensations, such as soft touch, whereas other neuron types are responsible for transmitting pain.

The researchers in Sweden discovered that nerve damage can cause the sensory neurons, previously unrelated to pain, to start transmitting pain signals.

How this occurs is down to a family of small RNA molecules known as microRNA. These snippets of code do not translate into proteins; instead, they are involved in regulating the expression of other genes. In particular, it is the MiR-183 cluster of microRNAs that are at work.

MiR-183 microRNAs have previously been shown to reduce neuropathic pain, but the mechanisms behind this effect had not been uncovered.

This new study demonstrated that, following injury, levels of these microRNAs drop, causing an increase in a certain type of ion channel. This hike in ion channel density switches the sensory neuron into a pain-transmitting neuron.

Our study shows that touch-sensitive nerves switch function and start producing pain, which can explain how hypersensitivity arises. MicroRNA regulation could also explain why people have such different pain thresholds.”

Prof. Patrik Ernfors, Department of Medical Biochemistry and Biophysics, Karolinska Institutet

Currently, gabapentin is often used to treat nerve pain, and although it works in around half of patients, its mechanism of action is not known. The researchers found that gabapentin works on touch-sensitive neurons. It blocks the ion channels that are increased as microRNA levels drop, effectively preventing the switch of roles from touch to pain transmission.

Prof. Ernfors is excited about the findings. He says, “What’s interesting about our study is that we can show that the RNA molecule controls the regulation of 80 percent of the genes that are known to be involved in nerve pain. My hope, therefore, is that microRNA-based drugs will one day be a possibility.”

Although the primary study was conducted in a mouse model, the team carried out some work on humans to check whether the same interactions were present. The results backed up the findings in mice.

Tests on human tissue demonstrated that regions with lower levels of microRNA were accompanied by higher levels of the particular ion channel, and vice versa. Although not definitive, this suggests that a similar mechanism is in place.

Because current drug treatment for nerve pain is inadequate, this study gives an interesting new approach for drug companies to trial. As Prof. Ernfors says, “The pharmaceutical companies have concentrated heavily on substances that target ion channels and receptors in pain neurons, but our results show that they might have been focusing on the wrong type of neuron.”

Further research in humans will be needed to confirm the findings, but better treatment for these mysterious conditions might be just beyond the horizon.

Learn how microRNAs give clues to schizophrenia’s auditory symptoms.