Scientists have found a substance that activates pain along the central nervous system, which is also able to decrease pain in the peripheral nervous system.

It was named Substance P, and it may be the reason why many pain management drugs appear to be successful amid laboratory tests and unsatisfactory in real-life circumstances. The study was published in the journal Antioxidants and Redox Signaling, on June 15. It explains how scientists from Hebei Medical University in China and the University of Leeds in the U.K. Came across Substance P, a peptide that promotes pain responses of different kinds through the nervous system.

How does pain looks like?
The finding of Substance P may provide an answer to two decades of failed clinical trials. Image credit: Science in Public.

Substance P controls pain

Substance P is synthesized in all of the nerves that send signals from and towards the brain and the spinal cord. The peptide desensitizes nerve cells, which causes a reduction of pain when it acts in the peripheral nervous system. In contrast, it stimulates neurons and causes a more elevated response towards pain, when it is found in the central nervous system.

Lead researcher, Professor Nikita Gamper from the University of Leeds, said that previous investigations indicated that Substance P always promoted pain. Now it seems that its function depends on the nervous system in which it is found. It can also act as a painkiller when found in the peripheral nervous system.

“This means that when drugs were used in trials to suppress Substance P’s action in the central nervous system, they may have also prevented it from acting as a painkiller in the peripheral system. So, although the drugs looked like they worked in the lab when they moved to clinical trials, they failed,” stated Gamper to eScienceNews.

Substance P: how it works

The zinc on neurons reduces neural responses. Substance P makes certain proteins very sensitive to zinc, which in part are in charge of allowing neurons to sense pain.

Gamper noted that understanding how Substance P works would allow doctors to prescribe drugs that are much more effective and less dangerous than most existing painkillers like morphine. The latter might cause addiction in most patients.


This finding comes to light just as America undergoes a severe prescription drug crisis. Image credit:

Developing a drug that copies Substance P’s chemical composition, while also not being able to pass the blood-brain barrier towards the central nervous system, could lead to a pain reduction alternative with very reduced side effects.

If the resulting drug can stay within the peripheral nervous system, and thus causing a natural and healthy reduction of pain, it is unlikely that the patient would develop any addiction, as it won’t affect the brain’s dopamine and endorphin receptors.

The first applications of Substance P will most likely be focused on punctual pain, but researchers believe that a drug can be synthesized in such a way that it can be used on a daily basis.

Source: eScienceNews