Pain Paradox: Why Some Painkillers are Not Very Effective During Clinical Trials

A new study revealed that a natural substance that is known to activate pain in the central nervous system is also causing an opposite effect in the other parts of the body.

The study, published in the journal Antioxidants and Redox Signaling, suggests that the Substance P is capable of making nerve cells less responsive and excitable leading to the reduction of pain sensations.

"We were really surprised by the results - Substance P is described in the literature as a molecule that gets nerve cells excited and promotes pain. But we've discovered a paradox - that in the peripheral nervous system it acts as one of the body's natural painkillers and actually suppresses pain," explained Nikita Gamper, a researcher from the University of Leeds and lead author of the study, in a statement.

According to the study, Substance P acts as a painkiller in the peripheral nervous system by modulating the action of certain proteins that control the ability of pain-sensing neurons to respond to 'painful' stimuli. One type of protein produced by Substance P is extremely sensitive to zinc, making that natural circulation of zinc in the circulation enough to dampen their activity and suppress neuronal responses.

Researchers believe that because of the pain paradox of the Substance P, some of the painkillers that are effective in lab settings, become not very effective in clinical trials. Drugs developed for the trials are capable of suppressin the action of Substance P. However, this drugs can also prevent Substance P from acting as a painkiller in the peripheral system.

Gamper and her team noted that their discovery of the pain paradox can open up new doors in the development of better painkillers with lesser negative side effects associated with stronger painkillers.

The study was conducted in a lab and in animal models. For the study, the researchers focused only on acute pain, but they plan to look at the role of Substance P in chronic pain as well.