‘Pain Paradox’ Discovery: Does It Offer Route to New Pain Meds?

‘Pain Paradox’ Discovery: Does It Offer Route to New Pain Meds?

A substance known as “Substance P” activates pain in the central nervous system, and researchers have found that it has the opposite effect in other body parts, which may pave the way to new methods of pain control.

In a study by the by the Hebei Medical University in China and the University of Leeds in the UK, researchers found that Substance P makes nerve cells less responsive and excitable in the peripheral nervous system, which reduces sensations of pain.  The authors noted that “this is in direct contrast to its role in the central nervous system, where it triggers very different signals, exciting neurons and so promoting pain.”

The study may shed light on the reasons why so many clinical trials of potential pain-killing drugs that targeted Substance P have been failures.

“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,” lead researcher Professor Nikita Gamper, from the University of Leeds, explained.

“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,” Professor Gamper added.

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

Professor Gamper stated that this discovery could open the door to new drugs that don’t have the negative side effects currently associated with stronger painkillers.

“Drugs like morphine hijack the 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,” says Professor Gamper.

“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 looked at the action of Substance P within nerve cells in the lab and in animal models, focusing on acute pain, but the researchers intend to look at its  focused on acute pain, but Professor Gamper aims to look at its role within chronic pain as well.

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Authored by: Staff

There are 5 comments for this article
  1. Emily Raven at 11:16 am

    Re: imaging and PT

    Please look up Ehlers Danlos and Marfans along with related conditions. Imaging can be completely normal but it is not JUST muscle pain by a long shot. Your comments here while nobody suffering with pain believes them are very hurtful for those like myself for outsiders to read and believe. YOUR experiences while valid do not dictate outcomes for MINE nor anyone else’s. Thanks.

  2. mark nawrot at 9:43 pm

    Re:Substance P , Dr. Stephen Rodriguez
    Obviously you have never suffered from severs chronic pain, pain so bad that one wants to stop living. One day you will need a heavy duty pain killer , and I hope your doctor says to you,,, pain killers won’t help you,,, you need PT!

  3. Stephen Rodrigues, MD at 9:22 pm

    Substance P is too imaginary, office-based insignificant and betrays what we know about pain. (But deny for profits)

    The known laws of nature and human biology are that the most common location of long-term pain is within the muscular system.
    The pathology of this pain is called microscopic scars.
    These so-called microscars can only be treated with time and effort applied to physical labor as in physical therapy.
    This is because these micro-scars will not benefit from surgery or medications.
    In actuality, it’s impossible for these micro injuries to benefit from any interventional surgical procedure or medication.
    Surgery should be but is not reserved, for removing solid objects which cause pain.
    Medications should be but is not reserved, for treating certain conclusive laboratory pathologies.

    This flawed idea of treating long-term pain with painkillers on drugs was started over 100 years ago with Coca Coke and aspirin.
    Using drugs to treat micro scars has never worked and will probably never work.
    It is ill advised to try and cheat mother nature out of the PT treatments which are perfectly designed to benefit intramuscular micro scars.
    You can’t fool mother nature. You can’t trick mother nature.
    If you deny mother nature PT for muscle pain, you will suffer miserably or die.

    Physical therapy is the treatments for all bodily injuries.
    Here are some examples of physical therapy pain problems: fractures, contusions, collisions, sprains, strains of work, sporting events, fun, and play.

    The use of painkillers should be considered supportive in nature and non-therapeutic.
    Nonsteroidal anti-inflammatory medications are only supportive and non-therapeutic.
    One of the worst medicines to give someone who has long-term pain are narcotic painkillers because they mask the pain, give a false sense of security and then you have the problem of dependency addiction, overdoses, and suicides, etc.

    Medications work perfectly for sinus infections, ear infections, throat infections, urinary tract infections, Gout, Rheumatoid Arthritis, Systemic Lupus Erythematosus and the like.

    Drugs which do not work for diagnoses which use a Xray, MRI with blood testing negative must be muscular. PT is then the treatment of choice.

  4. mark nawrot at 4:56 pm

    Making a drug to affect certain nerves in the body? Good luck with that. And as for side effects of opiods, when is addiction listed as a side effect of opiods? Besides sleppiness, you left out constipation, which I’m having more of a problem with on Tramadol, a synthetic of vicodan. I was on vicodan for 4 years, stable dose, NO addiction, now, I live in pain, and have no quality of life. Have peripheral neuropathy, started in 1995 due to antiviral drugs for HIV. Eight years ago had to switch to 5 new antivirals, 4 of which can cause diabetes. Guess what, I’m now diabetic, and thst has caused neuropathy to get really bad fast in the last 4 -5 years. I wouldn’t wish this pain on my worst enemy. Have even considered stoppi g my antivirals, I mean , at this point , what’s the point.

  5. Tim Mason at 4:56 am

    I love stories like this. It is all chemistry. It is chemists that have provided the medical community with all the advanced tools they rely on today. Every thing from new fangled medicine to advanced diagnostic tools.
    One crippling back disease that older people get (5 in 1000) is spinal stenosis. 100 years ago we only new it as an old person disease. We now have the tools to understand it as narrowing of any three areas in the spinal process. Of course we have to add the scientific term “stenosis”
    Thank you Staff.