Chronic pain, the hidden fault in the brain

Like a car, the brain would also have a kind of driver capable of guiding reactions to pain. When we get pricked or burnt or otherwise experience acute pain, the nervous system would activate a kind of brake that would gradually dampen the reaction. But the same would not happen when the pain becomes chronic. In this situation, the pain signals would not be able to be switched off and would therefore remain active. And without any particular possibility of being corrected.

The automotive metaphor, of course, is not really scientific. But it may help to understand how much and how research appearing in Science Advances could help to find new approaches to chronic pain, one of medicine's most complex challenges. In fact, the study sheds light on this scientific 'secret' that is allegedly hidden within the brainstem, a region of the central nervous system, and more precisely in the medullary dorsal horn. In short, it adds an important piece to the mosaic of knowledge. So much so that, by focusing on the specialised neurons in this area, the prospect of future targeted therapies has been raised. Of course, we are only at the beginning. But there is hope of getting to act on the abnormalities of the braking system, which does not function as we would like, perpetuating the pain over time.

The research, co-ordinated by Ben Title and Alexander M. Binshtok of the Hebrew University-Hadassah School of Medicine and the Center for Brain Sciences (ElscL) of the Hebrew University of Jerusalem, focuses on the invisible systems that govern the control of pain circuit signals, because these would behave differently depending on the type of pain. All because of the reaction of a specific area of the brainstem in which neurons are located that are true 'stations' along the pathways travelled by pain signals.

What happens when, for example, we have the classic pain of passing arthritis or a stiff neck? In these cases, this spot of nerve cells reduces its activity and thus, just like a brake, helps to control the amount of stimuli that are sent to the brain. Then, as soon as the pain and inflammation subside, perhaps also thanks to the action of therapies for acute symptoms, the neurons in this area return to their normal activity. The problem is that in chronic pain all this delicate system does not work properly, with the neurons that, mistakenly, instead of limiting their action, tend to become even more excitable and thus, in some way, are themselves the 'fuel' for maintaining the pain.

The study, as the university note notes, also explains the mechanism by which neurons would alter their excitability. Everything would be linked to a specific potassium current, defined as type A, which has the task of favouring the regulation of neuronal excitability. Beware, however: if in acute pain this current increases, acting as a natural sedative, in chronic pain it does not increase and therefore neuronal hyperactivity occurs. In short, a regulatory mechanism that appears to be of great importance is missing, according to the study. Stopping this control system could turn into a real biological switch that changes, leading acute pain to become chronic. As the university reports in a note, the study could open up important perspectives in terms of therapies for these forms of pain. 'This is the first time we observe how the same neurons behave so differently in acute versus chronic pain,' Binshtok comments in the paper. 'The fact that this natural 'calming' mechanism is absent in chronic pain suggests a new therapeutic target. If we can find a way to restore or mimic that braking system, we may be able to prevent pain from becoming chronic'.