Neuronal Circuit Likely Behind Chronic Itch in MS and Other Diseases Identified

Neuronal Circuit Likely Behind Chronic Itch in MS and Other Diseases Identified

The nerve cell circuit, stretching from the skin to the spinal cord, that is likely responsible for the persistent itching sensation  that can afflict people with multiple sclerosis (MS) and other conditions was identified in a study.

The discovery was made in mice and as such is still preliminary, but researchers say this work may lead to specific treatments for chronic itch.

The study “Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch” was published in the journal Neuron.

People with MS can experience a range of altered and unpleasant sensations — frequently described as a tingling, itching, burning or aching feeling, or a “girdling” sensation across the body (popularly called the “MS hug”). These sensations are collectively known as dysesthesia. They are caused by damage to nerves that perturbs the normal transmission of messages to and from the brain.

Chronic itch, that which lasts for six or more weeks, also troubles people with conditions such as eczema, nerve damage caused by diabetes (diabetic neuropathy), and cancer.

Patients can show extra sensitivity to what’s called mechanical itch — which normally comes from a light brushing or poking against the skin — as well as to persistent spontaneous itch. (Chemical itch, in contrast, is a response to things like an insect bite and linked to activation of the histamine system.)

The underlying neural circuits are not well-defined, and no effective treatments exist.

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Researchers at the University of Michigan investigated in detail the mechanisms behind chronic mechanical itch, looking for possible treatment approaches.

To narrow down which nerve cells (neurons) account for mechanical itch, they individually removed nine distinct groups of spinal neurons from mice.

One, called excitatory interneurons, had high levels of a protein called Urocortin 3 (Ucn3); these neurons were central for the transmission of both acute and persistent mechanical itch.

“Behavioral analysis after the ablations of these neuronal subsets revealed that Ucn3 neurons are the mechanical itch transmission neurons,” Mahar Fatima, PhD, a study co-author, said in a university news release.

Removing the other spinal neuronal groups did not “affect the transmission of mechanical itch,” Fatima added.

According to the team, a mechanical itch starts upon activation of specialized sensory cells found in skin, called Toll-like receptor 5-positive low-threshold mechanoreceptors. These cells react to a light touch, passing the message along to Ucn3 interneurons in the spinal cord.

Researchers also found a third important player, called inhibitory interneurons expressing neuropeptide Y (NPY). These nerve cells control Ucn3 neuronal activity; that is, they control how much skin “tickling” is needed to cause itching. In other words, the researchers said, these inhibitory interneurons are “the gatekeepers” of sensitivity to itch. If they are defective, a person could experience chronic itch.

To confirm that this neuronal circuit was indeed responsible for mechanical itch, the team manipulated mice to either lack Ucn3 neurons or to shut down their activity.

Mice so altered stopped responding to a light tickle behind the ear, even though they still reacted to a chemical that triggers itching. This indicated that the chemical and mechanical itch pathways are separate, and that Ucn3 neurons are solely contributing in the latter pathway, the researchers said.

In each of various experiments, the mice’s ability to sense touch, pain, or thermal sensation were not affected, demonstrating the specific role of these neurons in itching.

Further mice experiments suggested that under chronic itch conditions, NYP interneurons do not work properly, preventing Ucn3 neurons from stopping as they should, and making them more prone to being overactive.

This, the research team said, may explain why patients with chronic itch have heightened sensitivity and a tendency for persistent spontaneous itch. Consistent with this hypothesis, removing Ucn3 neurons from mice prevented mechanical itch sensitization and persistency in the animals.

“Itching is one of the major symptoms in most skin disorders and other neurologic disorders,” Bo Duan, the study’s senior leader, said. “This is one mechanism we needed to understand to develop a new treatment for patients with chronic itch.”

Ana is a molecular biologist with a passion for discovery and communication. As a science writer she looks for connecting the public, in particular patient and healthcare communities, with clear and quality information about the latest medical advances. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in genetics, molecular biology, and infectious diseases
Ana is a molecular biologist with a passion for discovery and communication. As a science writer she looks for connecting the public, in particular patient and healthcare communities, with clear and quality information about the latest medical advances. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in genetics, molecular biology, and infectious diseases
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  1. Cheri Clark says:

    I’ve been wondering if the drug Dupixent (not sure of spelling) would help relieve my horrible itching. Has anyone tried it or know anything about how it relates to MS itching?

    • Stacey says:

      I’ve had places from itching all down my spine for YEARS! Worse in the winter time.
      I’ve taken Dupixent 3x & all of a sudden my back is totally cleared up 😃
      My Doctor has put me on it for severe asthma. So far so good !

  2. Marsha Berman says:

    I have been treating my midsection itching with Gabapentin for several years. I take 600 mg tablets 4 times per day to keep it under control. Is there any other recommended treatment?

    • Linda Costanzo says:

      I have found that NasalCrom helps with the itching. I have Mastocytosis and Primary Bilary Cholangytis (a liver disorder) and itching became unbearable. Benadryl didn’t help. NasalCrom is for nasal symptoms of hay fever and it inhibits mast cells that cause hay fever’s nasal congestion. It is OTC and has helped me. It is a nasal spray. I use it 4 ow 6 x a day. No drowsiness. I researched itchiness and found this on my own. Doctor has approved. It is not a cure-all and I still take gabapentin also, but not when I have to drive; it makes mea little goofy.

  3. Carole Ginther says:

    I itch on all four limbs often after a shower since 1976. Water induced idiopathic urticaria has been Dx’d. Dx’d MS 2000.

  4. Kasha says:

    I’ve started taking CBD oil and haven’t had the biting/itching sensations on my legs for two months!! I no longer take Gabapentin.

    • Kathleen Knight says:

      How much cbd oil do u take?. I just starting taking it. Have had MS since 1992, And about a few months ago I started itching. Sometimes it feels like I have something crawing on me.

  5. Tammy Albanese says:

    Interestingly, I have horrible itching of my hands (palm) and feet (plantar surface aka bottom). My old neurologist said it was not MS related. I started to look for relief on my own and tried Zyrtec- lo and behold- IT WORKED! I spoke with my PCP about it and she said she as not surprised, it is what she recommends for patients who have itching and cannot tolerate Benadryl. Give it a try, it MAY work for you too. I will say if I miss a dose, I find myself using any hard surface I can find to relieve that itch, so it may take a few days to kick in.

    • Memorie says:

      I’ve horrible, chronic, all over body itching for years after taking antibiotics that I now believe I didn’t even need. The only thing
      I have ever taken for it is Zyrtec, and it works 100%.

  6. Katrina sween says:

    I was put on gavapenton for my nerve pain from a shoulder spane and impingement of the scapulas and I had a bunch of bad reactions and had to be tapered offf and after I was offf them completely this itching and almost like nerve pimples have been what I’m dealing with now

  7. Sam Adelstein says:

    I use hydroxyzine hcl 25mg tabs whenever I get these MS itching episodes.
    Usually one will work very nicely and on those days when it’s quite severe I will use 2.
    It does cause fatigue just like Benadryl but eventually our bodies will tell us when it’s OK to move forward versus when we have to just lay low. Just like any other day living with MS

  8. I have had the biting crawling sensation on my legs as long as I can remember. Now my arms right shoulder and palms itch all the time. even the top of my feet itch until I’ve scratched the blood from them. I have never been diagnosed for it correctly. My palms got so bad this summer they are cracked and its painful. I itch in my groin area until I scratch blood. I have been diagnosed with carpal tunnel, ulna nerve is pinched too, and last year Dr discovered a tumor growing on T1, what could be causing this? My father has Agent Orange and I wonder was it passed down to me.

  9. I take 10mg of hydroxyzine. My back has scars from scratching, and yes bleeding. The first time 7 years ago since my MD prescribed it, the itch goes away. I have to take it as soon as first scratch before histamine takes off.

    • Stacey says:

      I’ve had places from itching all down my spine for YEARS! Bled constantly, ruined my clothes, sheets, etc. always had scabs. Worse in the winter time.
      Absolutely NO meds helped;
      Benadryl, hydroxine, you name it I’ve tried it….

      Now I’ve started taking Dupixent shots, for asthma, (had 3) & all of a sudden my back is totally cleared up. No bleeding, no scabs. So far so good !

  10. Kim Ippolito says:

    The Answer for the itching that is caused by nerves is surgery to take the pressure off of the nerves in the spine. Disc surgery to remove the discs trapping the nerves with either fusion or a spacer.

  11. Margaret O'Neill says:

    I have MS. My Primary Care Physician and my Dermatologist both diagnosed the areas that itch differently. My Primary Care Physician calls my areas irritated by scratching, Eczema. My Dermatologist called it Notalgia Paresthetica. I scratch the area per intense itching, I notice the area scratched becomes elevated and hard. I scratch until I break the skin. Then the condition quits itching. It then scabs over, heals and the condition starts all over again. I have also been told that it could be caused by my Multiple Sclerosis. Who knows at this point in time ?

  12. Teresa says:

    I have been itching so bad lately all the places I can’t scratch been miserable I’ve been off my lryica for almost 2 weeks. Waiting to get enough to get my script up till now hasn’t been to bad but now I feel like I’m gonna go crazy

  13. Merle Evans says:

    I do not see any mention of internal (YES INTERNAL) itching. The session last for 10-15 minutes – ususally starts with small spot on hands itching the area gets larger and Scratching is useless. I have found some relief with cold water. I also have occasional bouts on my legs. I have the itch no one can see! (Even though it drives me crazy!)

  14. Scout Lyons says:

    I’m so scared. I’ve been dealing with uncontrollable itch mostly on my arms but shoulders as well. It’s hurting my skin. I’m hypersensitive to all touch. Could my chiropractor have damaged my nerves? Please someone give me advice all my doctors are baffled and I’m afraid I’m stuck like this.

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