Chemical Abnormalities in the Brain

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Emerging research suggests that fibromyalgia patients suffer from the inability to process pain correctly, possibly as the result of various chemical imbalances within the brain. For example, fibromyalgia patients suffer from what is known as central pain amplification, or increased pain from normally painful stimuli, as well as allodynia – pain from normally non-painful stimuli. These phenomena can best be understood by examining how the human body perceives and processes pain under normal conditions.

Our brains perceive pain through numerous types of nerve endings in our skin. When a painful stimulus touches the skin, these nerve endings convert the energy from the stimulus into an electrical impulse. This electrical impulse then travels along nerves until it reaches the spinal cord. Once at the spinal cord, it travels to the brain, where the brain perceives the impulse as painful and relays the sensation back to the rest of the body.

Neurotransmitters are a type of “chemical messenger” that carry pain signals (and signals from other stimuli, such as heat or cold) from one nerve cell to the next. The three main types of neurotransmitters that are involved in transmitting pain signals to the brain are known as substance P, NMDA (n-methyl-d-aspartate), and glutamate. When the body has extra amounts of these neurotransmitters, it is easier for pain signals to make it to the brain. Individuals with normal responses to pain produce adequate amounts of the neurotransmitters serotonin, dopamine, and norepinephrine, which help to regulate the release of glutamate and other pain-signal-carrying neurotransmitters. An appropriate balance between all of these neurotransmitters results in efficient and adequate pain signaling.

Evidence from recent studies has begun to demonstrate that fibromyalgia patients tend to have disproportionate levels of pain-regulating neurotransmitters (Lee et al., 2011), an imbalance which may likely contribute to the excess pain signaling that is now believed to contribute to the development of fibromyalgia. Coupled with the fact that fibromyalgia patients also have much lower pain thresholds than individuals without the condition, this imbalance sets up a cycle of heightened sensitivity to pain and increased pain signaling, and culminates in a cycle of chronic pain for the fibromyalgia patient. Studies have shown that fibromyalgia patients have higher levels of glutamate and substance P, and reduced levels of dopamine, norepinephrine (Lee et al., 2011; Wood et al., 2007), and serotonin (Lee et al., 2011; Frank et al., 2004; Mease, 2009).

Neurotransmitters in the Development of Fibromyalgia

Early studies that investigated the etiology of fibromyalgia found low levels of serotonin among fibromyalgia patients (Russell, 1989). In addition, Russell and colleagues also determined in a subsequent study that low levels of serotonin were inversely related to various clinical measures of fibromyalgia-related pain. In other words, the lower the serotonin level of the patient, the greater their perceived pain level (Russell et al., 1992). More recently, Frank et al. (2004) examined DNA samples from 48 fibromyalgia patients and found genetic variations in genes that regulate serotonin production. Although the authors note the preliminary and exploratory nature of their findings, they stress their importance for future research.

Beyond serotonin, more recent research has focused on the role of the neurotransmitter glutamine in the development of fibromyalgia. A 2010 study by Fayed et al. found that fibromyalgia patients had elevated levels of glutamine. In this study, patients with elevated levels of glutamine were also found to have poorer pain thresholds and higher scores on the Fibromyalgia Impact Questionnaire (FIQ), both of which suggest that elevated levels of glutamine are associated with the increased pain and tenderness experienced by fibromyalgia patients (Fayed et al., 2010). Similar findings related to glutamine were also recently reported by two other groups of researchers (Harris et al., 2009; Valdes et al., 2010).

This emerging evidence regarding the involvement of neurotransmitters in pain signaling, in particular serotonin, dopamine, and norepinephrine, may also help to explain why certain anti-depressants are often beneficial treatment for certain groups of fibromyalgia patients (Phillips & Clauw, 2011). Research has shown that antidepressant medications that increase the functions of serotonin and norepinephrine combined actually have analgesic (pain-relief) properties in fibromyalgia patients and work better than antidepressant medications that target only one specific neurotransmitter (Mease, 2009). For example, tricyclic antidepressants, such as amitriptyline, have historically been beneficial to many fibromyalgia patients, although their long-term use is limited due to significant side effects for many people.

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References

1.        Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states – maybe it is all in their head. Best Pract Res Clin Rheumatol. 2011;25(2):141-154.

2.        McCarberg BH. Clinical overview of fibromyalgia. Am J Ther. 2011;Feb 15:ePub.

3.        http://www.painandwellness.com/how-pain-works

4.        Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arth Res Ther. 2011;13:2011.

5.        Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007;25(12):3576-3582.

6.        Mease PJ. Further strategies for treating fibromyalgia: the role of serotonin and norepinephrine reuptake inhibitors. Am J Med. 2009;122(12 Suppl):S44-S55.

7.        Petersel DL, Dror V, Cheung R. Central amplification and fibromyalgia: disorder of pain processing. J Neurosci Res. 2011;89:29-34.

8.        Frank B, Niesler B, Bondy B, Spath M, Pongratz DE, Ackenheil M, Fischer C, Rappold G. Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients. Clin Rheumatol. 2004;23:338-344.

9.        Russell IJ. Neruohormonal aspects of fibromyalgia syndrome. Rheum Dis Clinics North Am. 1989;15:149-168.

10.     Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1992;19(1):104-109.

11.     Juhl JH. Fibromyalgia and the serotonin pathway. Alt Med Rev. 1998;3(5):367-375.

12.     Fayed N, Garcia-Campayo J, Magallon R, Andres-Bergareche H, Luciano JV, Andres E, Beltran J. Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate. Arthritis Res Ther. 2010;12:R134.

13.     Harris RE, Sundgren PC, Craig AD, Kirshenbaum E, Sen A, Napadow V, Clauw DJ. Elevated insular glutamate (Glu) in fibromyalgia (FM) is associated with experimental pain. Arthritis Rheum. 2009;60:3146-3152.

Napadow V, LaCount L, Park K, As-Sanie S, Clauw D, Harris RE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545-2555.

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Vanessa March 6, 2013 at 10:08 pm

I was diagnosed with Fibromyalgia in 1991 by a Rheumotologist and was excted about Dr. Jon Russell’s research at the University of TX way back in the early 90′s. It was a hugh break through to me. Then…..I heard nothing about it for years. Doesn’t the fact that we have elevated levels of substance “P” and human growth factor prove that the pain’s NOT imaginary?? That there really is a basis for the pain? And why did it take so long for neuropathic pain blockers to be perscribed for us after his research was published??? I went on Cymbalta in 2004 and it is like a miricle for me. Why did it take so long??

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