How Hyperactive Microglial Cells Are Linked to Chronic Pain

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.

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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!

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. View Profile