From the Skin Tissue to the Brain

It all signals pain!

How can you hurt from head to toe? Research shows the pain control system in the skin, spinal cord, and brain of fibromyalgia patients is overloaded, offering a reason for why you ache all over. In particular, immune cells that generally do not cause pain contribute to the flu-like fibro symptoms that make your whole body hurt.

Nerve Fibers in Skin

Alterations in the way the central nervous system (brain and spinal cord) works are  believed to be a major cause of your fibromyalgia pain, but researchers are finding that’s not the only source. The immune cells surrounding the nerve endings in your skin appear to be contributing to your pain as well. Seong-Ho Kim, M.D. and colleagues in South Korea took tiny biopsies of the skin tissue from a group of fibromyalgia patients and compared them to healthy controls.¹

They found that most of the fibromyalgia patients, but none of the controls, showed enlarged or ballooned Schwann cells. These cells, which look like a string of sausage links, encase the nerve fibers that connect your spinal cord to peripheral tissues like your skin and muscles. These fibers relay information from your tissues to your spinal cord, and vice versa.

Under normal situations, Schwann cells provide nutritional support and protection for nerves. But since they are part of your immune system, they are always surveying the nearby environment to make sure nothing happens to threaten or harm your nerves.

Enlarged Schwann cells are in an activated state, usually triggered by infections and tissue injury. When activated, these cells pump out pain-causing chemicals to prompt your immune system to clean up debris and help repair damaged tissues. But in people with fibromyalgia, something unusual happens.

Although the Schwann cells are enlarged, there are no obvious signs of tissue injury in fibromyalgia patients’ skin. But everything is not normal. When their skin is examined under an electron microscope, the pain-producing chemicals secreted by the immune cells are present in high concentrations.² These chemicals, called cytokines, activate nearby nerve endings and make the skin hurt. Cytokines are also elevated in the blood and can cause flu-like achiness everywhere.

Faulty Pain Filter

In order for you to actually feel pain, transmissions from your skin, muscles and other tissues has to reach a level of consciousness in your brain. Otherwise, all sensations, including light touch, would hurt. That’s where your spinal cord comes in handy. The cord’s role is to filter out the less serious nerve signals traveling from your tissues to your brain and from your brain out to your tissues. In essence, your spinal cord works like a pain filter, but studies show it’s doing a poor job in fibromyalgia patients.

Kim’s team suspects that fibro patients have too many signals are traveling down through the cord to the tiny nerves in the skin, causing the fibers to become overstimulated. The Schwann cells attempt to keep pace by clearing out the waste products and debris, while providing nutrients to the overworked nerve fibers. In the process, they become enlarged.

How do ballooned Schwann cells impact your pain? They secrete pain-promoting cytokines that irritate nearby nerve fibers. The irritated nerve fibers in the skin then start relaying signals back to your spinal cord, saying, “Ouch … help me out!” But the cord fails to filter the signals and the brain shoots more transmissions back to the tissues. This process leaves you with painful skin, even though it looks normal. The same situation likely occurs in your muscles to make them ache.

Spinal Cord Opioids

When experiencing fibro pain, you would think the neurons in your spinal cord and brain would release lots of pain-killers to get your symptoms under control. Operating under this assumption, James Baraniuk, M.D., of Georgetown University, and Daniel Clauw, M.D., of the University of Michigan in Ann Arbor, measured the spinal fluid level of naturally produced opioid-like endorphins called enkephalins. They compared a fibro group to chronic low back pain patients (regional pain) and healthy pain-free controls.³

The concentration of enkephalins in the fibromyalgia group was almost fourfold greater than the controls, but pain alone was not the reason for this difference. The enkephalin levels were almost as high in the chronic back pain patients (people with less areas that hurt). This means a fibro patient’s spinal cord is pouring out natural pain-killers (e.g., enkephalins) to contain the pain, but it’s probably inadequate to relieve the many areas that hurt.

Opioid Receptors in Brain

You may wonder if the high concentration of enkephalins in the spinal fluid (which bathes the brain) are not properly activating the pain-relieving centers in your brain. After all, given the high concentrations of spinal opioids, you should not be in so much pain.

Clauw’s team measured the number of receptor sites in the brain that opioid-like substances target to put out the pain. He compared a group of fibromyalgia patients to a group of healthy controls using brain imaging.⁴

The fibromyalgia patients had fewer opioid receptors available in their brains to regulate pain. Why? Either the elevated amount of enkephalins (opioid-like substances) in the spinal fluid are monopolizing most of your brain’s receptors or there just are not enough of them to get your pain under control.

So Why Do You Hurt?

Assuming you are producing plenty of opioid-like substsances to target the pain-relieving receptors in your brain, why do you still hurt all over? Researchers don’t know all the details, but the foregoing findings offer some important clues.

Studies show the skin is a source of continuous pain transmissions traveling to your spinal cord. The cytokines produced by enlarged Schwann cells cause local irritation, which would be expected for injuries or infections, but there is no evidence of destroyed tissue in fibro. Yet cytokines continue to be produced for unclear reasons, causing your flu-like achiness.

Substantial elevations of the opioid-like enkephalins in your spinal fluid could be doing more than trying to provide analgesia. They might also be activating the immune cells in your spinal cord to produce pain-promoting cytokines, and one study indicates this is the case.⁵

Your body is trying to put out your pain by producing large amounts of opioid-like endorphins (e.g., enkephalins). But opioids don’t just relieve pain, they also activate immune cells to release cytokines to help heal injuries (usually a temporary process). Despite no signs of tissue destruction in fibro, your immune system seems to think there is. This means your body’s attempts to ease discomfort backfires (e.g., the pain-promoting cytokines win out over the opioids), leading to more rather than less pain.

1. Kim SH, et al. Clin Rheumatol 27:407-11, 2008.
2. Salemi S, et al. J Rheumatol 30:146-50, 2003.
3. Baraniuk JN, et al. BMC Musculoskel Dis 5:48-54, 2004.
4. Harris RE, et al. J Neurosci 27:1000-6, 2007.
5. Kadetoff D, et al. J Neuroimmunol 242(1-2):33-8, 2012.

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