Does 'Pain paradox' discovery directs to new pain control drugs?

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Does 'Pain paradox' discovery directs to new pain control drugs?

A natural substance known to initiate pain in the central nervous system has been found to have the opposite effect in other parts of the body, potentially leading to new methods of pain control. The finding could explain the repeated and costly fiasco over the last 20 years of clinical trials of potential pain-killing drugs that targeted the substance called as 'Substance P'.

Substance P is generated in both the central nervous system (CNS) and in our peripheral nervous system (PNS), all the other nerves and nerve cells that convey signals to the brain.

A research by Hebei Medical University in China and University of Leeds in UK revealed that sensations of pain are reduced when Substance P makes nerve cells less responsive and excitable in peripheral nervous system. This is in disparity to its role in the central nervous system, where it triggers very different signals, exciting neurons and so encouraging pain.

According to Professor Nikita Gamper, a lead researcher from the University of Leeds, "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 have discovered a paradox that in peripheral nervous system it acts as one of the body's natural painkillers and actually suppresses pain."

"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." Substance P operate in peripheral system by modulating the action of certain proteins that control the ability of pain-sensing neurons to respond to 'painful' stimuli. Substance P makes one type of these proteins extremely sensitive to zinc, so that natural levels of zinc in circulation are enough to dampen their activity and repress neuronal responses.

Professor Gamper also mentioned "Drugs like morphine hijack body's natural painkilling mechanisms, such as those used by endorphins, but because they act within the central nervous system, they can affect other brain cells that use similar pathways, leading to side effects such as addiction or sleepiness. If we could develop a drug to mimic the mechanism that Substance P uses, and ensured it couldn't pass the blood brain barrier into the CNS, so was only active within the peripheral nervous system, it's likely it could suppress pain with limited side effects."

The study which inspected the activity of Substance P within nerve cells in the lab and animal models- focused on acute pain, but Professor Gamper aims to look at its role within chronic pain as well.

University of Leeds
Exploratory, Substance P, Pain, Neurotransmitter, Review
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