Neurology Central

Newly discovered mechanism may exacerbate chronic pain

A researcher at the University of Texas at Dallas (TX, USA) has discovered a new neurological mechanism that appears to play a role in inhibiting pain. The study, recently published online in Pain, focused on the biochemical reactions that lead to a reduction in certain neurological activity such as pain.

Previous research on inhibitory networks has focused on the activity of the GABA neurotransmitter that acts to inhibit neuronal activity. Strong evidence exists that suggests a process termed GABAergic plasticity is initiated when acute pain becomes chronic, causing GABA to lose its inhibitory function and so exacerbating the level of painexperienced.

The cause of the loss of inhibitory function, and replacement with excitatory actions, has so far been largely attributed to chloride ions. However, this study found another potential cause of GABAergic plasticity, a synaptic adhesion protein termed neuroligin-2.

Those suffering from chronic pain often don’t obtain the reduction in pain benefits that are delivered by the body’s inhibitory networks; instead they often experience an increase in pain.

Dr Ted Price, associate Professor in the School of Behavioral and Brain Sciences at the University of Texas at Dallas (TX, USA) explained:”When you hit your hand with a hammer, almost everybody has the same reflex reaction – that is, to rub your finger which, in turn, helps to reduce pain. The reason that works is because it increases GABAergic inhibition in the spinal cord. However, people who have chronic pain – if they do the same thing – find that rubbing it actually makes the pain worse. That’s because the GABAergic system loses its efficacy and, in fact, can become excitatory.”

Importantly, the work provides another hypothesis for the mechanism behind the malfunctioning of the GABAergic system in individuals with chronic pain.

“Having two ideas and different models will allow us to determine what the therapeutic opportunities are – creating something that will change that back to normal. The lack of performance in the inhibitory system is very detrimental to those who are in chronic pain,” commented Price.

Price described the development of chronic pain as the body ‘learning’ that something is bad.

“It’s changing the way the body functions – it’s learning. That learning, in the case of chronic pain, is aberrant – it’s causing the situation to get worse. If we can figure out what that form of learning was, then we can potentially reverse it. Understanding that the GABAergic system changes during this form of learning potentially offers a new therapeutic avenue,” he remarked.

Although these findings won’t immediately lead to new pain therapies, they do offer a potential new therapeutic direction for future investigation.

Source: University of Texas at Dallas