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'Pain paradox' may lead to more effective pain treatment

A substance in the body works one way in the central nervous system and another in the peripheral nervous system, explaining why some experimental drugs work in the lab but not in human trials.

By Stephen Feller
'Pain paradox' may lead to more effective pain treatment
With a new understanding that a substance in the body involved with the sensation of pain works differently in the peripheral and central nervous systems, researchers say more effective pain control methods are possible. Photo by Albina Glisic/Shutterstock

LEEDS, England, July 28 (UPI) -- A substance that activates pain in the central nervous system was found by researchers to also reduce pain in the peripheral nervous system, a finding researchers say is surprising but could help improve methods of pain management.

Researchers in England and China discovered the paradox of Substance P, which they say explains why some pain control drugs work in the lab but not in clinical trials, according to a recent study published in the journal Antioxidants and Redox Signaling.

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Substance P is a peptide that in the central nervious system excites nerve cells and promotes pain responses, but in the peripheral nervous system acts like a natural painkiller. This, researchers say, is why efforts to suppress it in the central nervous system also suppress it in the peripheral nervous system, promoting pain.

Morphine is an effective painkiller because of its action in the central nervous system, where it uses the body's natural painkilling ability, but it affects other functions because it is operating in the brain -- leading to sleepiness or addiction, among other side effects.

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"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," Dr. Nikita Gamper, a professor at the University of Leeds, said in a press release.

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The discovery was made while studying Substance P in nerve cells in lab dishes, as well as in rats, focusing on acute pain. The researchers say one type of protein Substance P interacts with is highly sensitive to zinc, with small amounts able to decrease the protein's action and suppress pain.

The challenge, researchers say, will be to find a way to affect what Substance P does in one part of the body, but not in the other. Future research also will have to focus on chronic pain, which manifests differently than acute pain.

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"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," Gamper said.

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