How Hyperactive Microglial Cells Are Linked to Chronic Pain

by Chris Centeno, MD /

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How do your nerves stay healthy? That’s a big question that’s at the heart of everything from peripheral neuropathy to Alzheimer’s disease. What happens when the waste removal cells go bad and how is that linked to chronic pain? This morning I’ll review a concept that’s emerging in neuroscience that interfaces with cell therapy. Namely, that forgotten cells in your central nervous system can go bad and set off a conflagration of chronic pain much like throwing gasoline on a campfire.

Pac-Man Cells are Everywhere in Your Body

Your body has “Pac-Man” cells that get rid of waste, such as dead or damaged cells, tissue, and foreign invaders. They do this by literally gobbling up the bad stuff, just like a Pac-Man eating those little dots. These Pac-Man cells are called macrophages, and they have cousins in the brain, nerves, and spinal cord called microglial cells. Microglial cells are immune cells that live alongside neurons (nerve cells) throughout the nervous system and provide support and protection to maintain a healthy nervous system. They do this just like their macrophage Pac-Man cousins in that they gobble up the bad stuff. In fact, it’s now thought that one reason we develop diseases like Alzheimer’s dementia is that the microglial cells get overwhelmed with too much waste and the area becomes toxic to the local nerves.

Microglial Cells and Sensitized Nerves

Microglial cells usually lie dormant near a nerve cell until we experience an injury or a foreign invader arrives, which creates inflammation. Inflammatory cytokines switch on—or activate—our microglial cells, and they swoop in to address the problem, devouring bacteria, plaque, and other debris as they go. When the pain and inflammation are acute and the inflammation subsides, the cells deactivate and return to their dormant state, and all is well. However, when pain and inflammation become chronic, microglial cells can stay active too long and become hypervigilant. In this state, they release chemical signals that ramp up the nerves, causing sensitization. This means that the nerves are set off by the slightest stimulus. We now have a huge body of scientific literature that supports that sensitized nerves are the cause of many chronic pain conditions.

In chronic pain, sensitization then spreads from cell to cell, like a domino effect, as more neighboring microglial Pac-Man cells activate. This continues from the injured area to the center of the body, with each activated microglial cell ramping up its zone of local, associated nerve cells, spreading all the way from the peripheral nerves to the spinal cord and then up to the brain, leading to chronic pain through these sensitized nerves. This can explain why even a gentle touch can be painful in the presence of chronic pain.

Incidentally, chronic inflammation even in cases of obesity, for example, can keep inflammatory cytokines coursing through the body, which keeps macrophages switched on and in hyperactive mode, striking out at anything in their path. This can lead to diabetes, heart disease, and even stroke. In addition, the accumulation of macrophages in fat is believed to be a key player in metabolic syndrome.

So Are Pac-Man Cells Good Guys or Bad Guys?

It depends. Microglial cells and macrophages can have positive or negative effects. Last week, for example, we looked at how our microglial cells, when functioning properly, may play a part in delaying dementia. On the other hand, Pac-Man macrophage cells can become activated in arthritis, for example, and begin gobbling up not just damaged tissue but normal cartilage as well, but research has shown that mesenchymal stem cells can deactivate these rogue macrophages and prevent them from further cartilage destruction.

In fact, based on the concept of rogue microglial cells causing chronic pain, there are a couple of reasons stem cell therapy may have a role in treating chronic pain:

  1. Mesenchymal stem cells can deactivate activated microglial cells and macrophages.
  2. Bone marrow hematopoietic stem cells can replace worn out or overburdened microglial cells.

The upshot? When our microglial cells are on their best behavior, they can keep us healthy by attacking foreign invaders and gobbling up all of the toxic debris in our nervous system. When chronic injury and inflammation spirals their behavior out of control, microglial cells can wreak havoc on our nerve cells, causing hypersensitivity and more pain. All the more reason to do all we can to keep pain and inflammation in check!

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2 thoughts on “How Hyperactive Microglial Cells Are Linked to Chronic Pain

  1. Robert Levin

    Hi
    Sorry my question has nothing to do with this post. If possible put into the right post or pass it on to Dr. Centeno
    The question I have has to do with Statin’s. I was on a very low dose of Vytorin 10/20 with is simvastatin / Zetia (excuse my spelling) for many years after having a stent put in 13 years ago(no heart attack or angina, had a 95% blockage in the mid LAD. I was taking 1/2 3 times a week for a long time. My total cholesterol was 136 and my LDL was down to 55. HDL was 60. The cardio doc was thrilled. I also take very good care of myself. Great diet and exercise. 5″10″ 160 lbs. and 70 years old.
    About 6 months to a year ago my knees starting hurting worse than usual and started having extreme muscle weakness. Stopped the statin 4 months ago and felt a lot better.
    Had my 1st blood test yesterday and my total cholesterol went up to 165 – LDL went to 90 and hdl is 65.
    My question to you is: What do you know about Red Rice Yeast as an alternative to the pharma statins?
    Do you have any thoughts on the new blood thinners, Eliquis etc. I have rare A fib (maybe once or twice a year and will normally only last a few hours?
    I do not want to take either drug. The Eliquis also caused some muscle issues?
    Sorry for the long question.
    By the way I did a have your stem cell procedure down in sw fl. Shoulder.

    Thank you
    Robert

    1. Regenexx Team Post author

      Robert,
      The decision about whether to be on statin cholesterol meds is for you and your cardiologist to make. Our concern is in the presence of statins, stem cells do not do what they’re needed to do, which is why we ask patients to get clearance to be off them for the requisite amount of time when getting a stem cell procedure. Sometimes, that clearance is not granted and patients need to know that will likely affect outcome.
      On Red Rice Yeast, truth being stranger than fiction, it has the identical active ingredient as Statins do! Eliquis has it’s share of side effects as all these drugs do, muscle and nerve issues among them. But only a physician with whom you have a Doctor patient relationship can advise you n whether the benefit of any given medication in your particular case, is worth the risk.

Chris Centeno, MD

Regenexx Founder

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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