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Why Head to Toe Pain

From the Skin Tissue to the Brain

… it all signals pain!

How can you hurt from heat to toe? Research shows the pain control system in the skin, spinal cord, and brain of fibromyalgia patients is overloaded and offers a reason for why you ache all over.

Nerve Fibers in Skin

Your central nervous system (brain and spinal cord) is believed to be a major player in causing your fibromyalgia pain, but it’s not the only one. The skin appears to be contributing to your pain as well. Seong-Ho Kim, M.D., and colleagues in South Korea, took tiny biopsies of this peripheral tissue from a group of fibromyalgia patients and compared the results to healthy controls.1

Most of the fibromyalgia patients, but none of the controls, showed enlarged or ballooned Schwann cells surrounding the nerve fibers. Schwann cells are part of your immune system and encase all fibers extending from your spinal cord to your peripheral tissues, such as your skin. These nerve fibers relay information from your tissues to your spinal cord, and vice versa.

Under normal situations, Schwann cells provide nutritional support and protection for your nerves. But keep in mind they are part of your immune system, always surveying the nearby environment to make sure nothing occurs that might be threatening to your body. These cells are geared to respond quickly to anything that is not quite right.

Enlarged Schwann cells represent an activated state usually triggered by infections and tissue injury. When activated, they pour out pain-promoting substances, called cytokines, to clean up the debris from the tissue injury. Yet, obvious tissue injury is not apparent in fibromyalgia. However, cytokine levels in the skin of fibromyalgia patients have been shown to be elevated when examined under the high-power magnification of an electron microscope.2 These chemicals can cause painful skin irritation.

Ordinarily, the central nervous system (particularly the spinal cord) is suppose to filter out the number of signals traveling to the tiny nerves in the skin. But this pain filtering system in the cord is not working well in people with fibromyalgia.

Kim’s research team suspect that too many signals are traveling 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 providing nutrients to the nerve fibers, and in the process, they become enlarged.

But the real question is, how do the ballooned Schwann cells relate to your pain? They secrete pain-promoting cytokine substances that irritate nearby nerve fibers. As a result, you are left with burning, itching skin, even though it looks normal. Your irritated nerve fibers in the skin start relaying signals back to your spinal cord, saying, “Ouch … help me out!” but this just makes matters worse in the cord.

Spinal Cord Opioids

When experiencing fibro pain, you would think the neurons in your spinal cord and brain would release lots of opioid-like pain-killing substances 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 levels of enkephalins in the spinal fluid of fibromyalgia patients. Enkephalins are naturally produced endorphins, similar to opioids. The results in the fibro group were compared to 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 and threefold higher than the regional low back pain patients. This means your spinal cord is pouring out natural opioid-like substances in a valid attempt to contain your pain, but it is just not enough.

Opioid Receptors in Brain

You may wonder if the high concentration of opioid-like substances 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 any pain whatsoever.

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 a brain imaging technique called positron emission tomography (PET).4

The opioid receptors in the brain were almost completely occupied in the fibromyalgia patients, particularly in the areas known to regulate pain. So the higher amount of enkephalins (opioid-like substances) in the spinal fluid appear to be properly working on the brain’s receptors to control your pain.

Why Do You Hurt?

If you are producing plenty of opioid-like enkephalins and they are activating the pain-relieving receptors in your brain, why do you still hurt all over? Researcher don’t know all the details, but the foregoing findings offer important clues.

Studies in the skin implicate it as a potential source of continuous pain transmissions traveling to your spinal cord and the cytokines produced by the enlarged Schwann cells cause local irritation. Substantial elevations of the opioid-like enkephalins in your spinal fluid could be doing more than hitting the centers in your brain to provide analgesia. They might also be activating your immune cells to produce pain-promoting cytokines. A recent study looking at cytokine levels in the spinal fluid of fibromyalgia patients supports this theory. One pain-producing cytokine was found to be increased fourfold.5

Your body is working overtime to put out your pain, and there is no question you hurt from head to toe, including your skin. However, too many pain-promoting cytokines appear to be produced by the opioid-related process. 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.

Curious about other symptoms caused by pain-promoting cytokines and your treatment options? This topic was covered in the Winter 2012 issue of the Fibromyalgia Network Journal. Get more with Membership. Learn about Member benefits.

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. [epub ahead of print] Nov. 27, 2011.

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