For those who have not read this yet (it was referenced in a post), the article is written in good layman's terms. It lays out the scientific and physiological aspects of FMS/ME but in a way that it understandable. Fibromyalgia - Ultimately a Disease of Amplified Pain by Mark J. Pellegrino, MD ImmuneSupport.com 05-26-2008 Advertisement Excerpted with permission from Chapter 9 of Dr. Mark Pellegrino’s very popular book, Fibromyalgia: Up Close and Personal.* Dr. Pellegrino has seen more than 20,000 FM patients in his practice at the Ohio Rehab Center, and has been a Fibromyalgia patient himself since childhood. Many conditions can lead to permanent changes in the pain transmission mechanism and result in chronic pain that overwhelms the body’s pain defense mechanisms. One such condition is Fibromyalgia. Fibromyalgia may not cause destruction along the pain pathways as other conditions I have mentioned can [rheumatoid arthritis, carpal tunnel syndrome, shingles, multiple sclerosis, for example]. However, Fibromyalgia does cause chronic abnormal changes along all the pathway components and this results in chronic pain via both peripheral (from skin, muscles and nerves) and central (from spinal cord and brain) neurological mechanisms. The end result of Fibromyalgia’s abnormal changes appears to be a state of pain amplification that cause severe generalized pain. Fibromyalgia is ultimately a disease of amplified pain. Dr. Robert Bennett has written and presented excellent information that explains why we hurt with Fibromyalgia (e.g., “Emerging Concepts in the Neurobiology of Chronic Pain: Evidence of Abnormal Sensory Processing in Fibromyalgia,” Mayo Clinic Proceedings). If we trace the pain signals through the various parts of the pain pathway (from the nociceptors - or specialized pain nerve endings – to the nerves to the spinal cord to the brain) in people with Fibromyalgia, we find various abnormalities along the way. Many studies have shed light on different points along the complete pain pathway. I want to briefly summarize some of these different abnormalities and possible problems encountered by Fibromyalgia pain signals on the path to the brain. NOCICEPTORS - Pain originates from the nociceptors Trauma is a common trigger of Fibromyalgia. Tissue injury - damage to the muscles and soft tissues – activates the nociceptors. Some studies have suggested that microscopic injury occurs in specific parts of the muscles (for those who want the medical names: muscle spindles, intrafusal fibers, and calcium pumps). Localized tissue injury probably activates arachidonic acid (a biological protein), which turns into “bad” prostaglandans (called Cox-II prostaglandins), and cause inflammation and pain. In addition to trauma, autoimmune factors may be another pain nerve activator. Perhaps autoimmune processes create compounds which act as irritants and activate the nociceptors chronically to the point where they become “permanently” sensitized and irritated. As a result, biochemical, hormonal, and red blood cell changes occur that interfere with the cells’ ability to receive adequate supplies of oxygen, glucose, and other nutrients. Blood flow, energy formation, and the cells’ electrical and neurological harmonies are all disrupted. Since the nociceptors remain “faulty,” the electrical and neurological balance remains abnormal, and nociceptors continue to be activated. Pain-producing neurotransmitters are released and accumulate as long as the nociceptors stay activated at the peripheral level (skin and muscles, especially). These persistent pain signals we experience may be interpreted as an itching, burning, swelling, or tingling at one end of the spectrum, or – at the other end – knife-stabbing, burning, or throbbing. One nociceptor can signal different pain signals and sensations depending on its level of irritation – the more irritated it is, the more severe the pain. These changes can become permanent and cause the nerves to become sensitized to the point where they are easily activated to send pain, even in the absence of any noxious stimulus. In other words, persistent pain signals can spontaneously arise from peripheral nerve endings and bombard the rest of the pain pathway. So, instead of waiting for outside stimulation such as trauma, pressure, temperature, or touch to signal the nociceptors, these nociceptors send pain signals on their own, without any outside help. This “spontaneous” pain is what we complain about the most! NERVES The nerves, especially the sensory nerves and the autonomic nerves, “wonder what is happening” because they are getting bombarded by all of these signals from the nociceptors. At first, they try to diminish these painful signals by using accommodation and gate mechanisms. However, the signals persist and they, too, undergo a sensitization process. They become hypersensitized and react with an exaggerated response instead of a normal or diminishing response (accommodation). Now we get even more pain, numbness, swelling, burning, and other sensations. Some of the hypersensitization may be mediated by nerve growth factor, which has been found in higher levels in Fibromyalgia. A high nerve growth factor may indicate the nerves are trying to regenerate or repair themselves. But instead of repairing the nerves so they act normal again, the opposite seems to happen. Nerve growth factor is probably enhancing the nerves’ abilities to transmit pain to the spinal cord. More pain results, not less. SPINAL CORD – Amplification, wind-up, allodynia, Substance P, generalization At the spinal cord level, the Fibromyalgia begins to take control. It is here that additional changes occur to perpetuate the pain and spread it to different levels. When pain generators first start firing, the spinal cord pain processing centers may act at first like a dry sponge and easily soak up all the signals. Our bodies may have many pain generators at any given time, but if they are slowly and intermittently firing, drug sponges can soak up the signals and not cause any bothersome symptoms. From time to time there may be an acute exacerbation of a problem leading to a lot of pain signals being generated, and if a lot of pain signals are dumped at once into the spinal cord sponge, only a little bit gets absorbed and a lot gets passed through and perceived as acute pain. In Fibromyalgia, however, the different pain generators continue to send signals and eventually the dry sponges becomes a wet sponge and it can’t soak up any more. The additional oncoming continuous signals will spill over the wet sponge, and this leads to persistent pain. The two main changes that occur at the spinal cord include: • Pain amplification (by specialized nerves called NMDA receptors) • And loss of pain filtering (by the diffuse noxious inhibitory control system). Spinal cord nerves are bombarded by continuous stimulation from the peripheral nerves, causing a progressive increase in electrical signals to be sent up to the brain. This phenomenon is called “wind-up,” and is the neurological mechanism for the amplification of pain. Once this wind-up phenomenon occurs, a central sensitization results in which various types of sensory signals - not just pain - will arrive in the spinal cord, become amplified, and be sent to the brain as pain. The spinal cord becomes more sensitized to sending pain, lots of it. Once this happens, the spinal cord is not able to properly sort out and filter various sensory signals. As a result, different sensory signals such as touch, pressure, temperature, and joint movement all become amplified and sent up the pain pathways, resulting in pain signals instead of the appropriate touch, pressure, temperature, or joint motion signals. This defect in pain transmission where there is increased sensitivity to all stimuli – even those which normally do not evoke pain – is called allodynia. Unfortunately for the person with Fibromyalgia, the spinal cord is now “wired” to interpret nearly all sensory signals as pain – severe pain! We can still appreciate touch, pressure, temperature, joint movement, and other non-pain signals, but pain contaminates these signals, and we feel the pain. Another key change at the spinal cord level is an increased formation of Substance P and other neurotransmitters. Substance P’s primary role at the spinal cord level is to transmit pain signals and to sensitize the spinal cord so it is readily available to transmit pain. When Substance P reaches high concentrations (as it does in Fibromyalgia), it can migrate up and down the spinal cord, away from the initial location of the pain signal. As a result, multiple levels of the spinal cord undergo sensitization and send increased pain signals, leading to a “generalization” of the Fibromyalgia. This spreading of pain explains how one can develop generalized Fibromyalgia from an initial regional area of pain. A common example of this occurs following a motor vehicle accident where a particular body part, such as the neck, was injured. Over time, the pain begins to involve the mid-back, low back, and ultimately the whole body, even though these areas were never injured. The Substance P-induced spinal cord changes can explain this migration of pain from the neck to the entire body. BRAIN Our poor brains have no chance, do they? Any pain memory stored in the past will be re-awakened by this process. Fibromyalgia is notorious for causing previously injured areas to hurt more once it develops. This previously injured area may have settled down and become essentially pain-free, but the pain memories remained, although inactive. Thanks to the Fibromyalgia pain amplification process, the inactive memories are reactivated. The pain centers of our brain, the limbic system and the cerebral cortex, are continuously fed these amplified signals from the spinal cord. Changes occur: • Serotonin levels decrease, • Brain waves change, • Sleep stages are affected, • Blood flow and glucose [blood sugar] metabolism are affected. The brain gets overwhelmed with these pain signals and spends a lot of attention and energy monitoring the pain. Fibrofog occurs. Emotional components are “attached” to pain, including fear, depression, anxiety, anger, hopelessness, and helplessness, which can further amplify the pain. In patients with Fibromyalgia, functional reorganization (brain plasticity) in both sensory and motor portions of the brain has been observed, and appears directly related to the chronicity of the pain (Dr. H. Flor, 2003). These brain changes may be viewed as pain memories that influence how painful and non-painful signals affect the body’s sensory and motor responses. The brain makes these changes to enhance its ability to perceive pain – brain amplified pain. This type of abnormal brain plasticity can be measured. Doctors Richard H. Gracely, Richard A. Harris, Daniel J. Clauw, et al. at the University of Michigan Chronic Pain and Fatigue Research Center have published studies which demonstrated abnormal “hyperactive” areas of the brains and abnormal “quiet” areas of the brains in Fibromyalgia test subjects who underwent functional MRIs. This provides objective evidence to support brain plasticity with both hypersensitive amplified pain, and turning off the ability to inhibit pain. FIBROMYALGIA PAIN SUMMARY To summarize, Fibromyalgia changes our pain pathways. It may start off as a peripheral irritant, but eventually it becomes a self-perpetuating process that affects the entire pathway from the nociceptors to the brain. The main problem, in a nutshell, is amplified pain. The amplified pain is the result of our nervous system gaining the ability to magnify pain and losing the ability to inhibit pain. What comes in at a signal of a “1” does not end up in the brain as a signal of a “1” as it would in people without Fibromyalgia. Our pain signal of a “1” gets amplified and magnified, and by the time it reaches our brain, it is a “10”! Other non-painful signals get thrown into this pain amplification pathway and arrive at our brain as pain signals. Even tiny subconscious pain signals can get amplified, or the nerve pathways can automatically “fire away” without any obvious noxious stimulus to cause spontaneous pain. These are not your everyday aches and pains, these are severe pains that cannot be ignored. This severe, chronic pain can completely disrupt one’s life. And by the way, while all of this is happening, we continue to look completely normal on the outside.