Clinical Hypothesis
Fascia: A missing link in our understanding of the pathology of fibromyalgia

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Summary

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia—and how it relates to other known abnormalities in fibromyalgia—remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation.

No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibromyalgia.

Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients.

The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia.

Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

Introduction

The etiology of fibromyalgia—a disorder characterized by widespread muscle pain and tenderness at specific soft-tissue tender points—remains unclear. However, in the past decade evidence for abnormal pain processing in fibromyalgia has significantly advanced our understanding of this disorder. In 2002, a functional MRI study demonstrated that it took much less thumbnail pressure in fibromyalgia patients to activate the pain sensing areas of the brain compared to controls (Gracely et al., 2002). Another study found that fibromyalgia patients experienced stronger pain and larger areas of referred pain after intramuscular injection of hypertonic saline (Sorensen et al., 1998). Other research has shown abnormal temporal summation and wind-up of pain in fibromyalgia (Staud et al., 2004). These findings demonstrate that in fibromyalgia the central nervous system has an exaggerated response to pain, a phenomenon called central sensitization.

Central sensitization is caused by repeated or sustained noxious input to the dorsal horn neurons leading to increased neuronal responsiveness or central sensitization. In fibromyalgia, however, no evidence of muscle pathology has been described, leading to speculation that the central sensitization in fibromyalgia may occur spontaneously though some as yet unknown mechanism (Ji et al., 2003).

Others argue that myofascial trigger points cause the central sensitization in fibromyalgia (Staud, 2008).

However recent biopsy studies have found increased levels of collagen and inflammatory mediators in the fascia of fibromyalgia patients. This paper proposes that dysfunction and inflammation of the intramuscular connective tissue, or fascia, leads to the central sensitization seen in fibromyalgia.

Section snippets

Central sensitization

Central sensitization, a state of heightened sensitivity in the spinal cord, is thought to be a physiologic adaptation of the nervous system to sustained painful input. It is the end result of a complex neuronal response to peripheral nerve injury or tissue inflammation. Recent studies support an important role for dorsal horn glial cells (support cells for neurons) and NMDA receptors in producing abnormal pain sensitivity in the spinal cord (Watkins et al., 2001, Dickenson and Sullivan, 1987).

What causes central sensitization in fibromyalgia?

Since patients with fibromyalgia complain of sore, painful muscles, investigators have long been searching for muscle pathology in fibromyalgia. These studies have included muscle biopsies with structural and ultra-structural observation, magnetic resonance imaging and metabolic studies, electromyography, and studies of blood flow and muscle strength. For the most part these studies have not shown consistent differences between healthy and fibromyalgia muscles. In Simm's rigorous review of 32

Background

The symptoms of fibromyalgia have historically been described by many different terms, including ‘Chronic Rheumatism’ and ‘Muscular Rheumatism’. In a review article in 1904, Stockman described the symptoms of chronic rheumatism as ‘pain, aching, stiffness, a readiness to feel muscular fatigue, interference with free muscular movement, and very often a want of energy and vigour’ (Stockman, 1904). Chronic rheumatism was not thought by Stockman to affect the joints themselves, but rather the

Fascia

Fascia is the dense connective tissue that envelopes muscles grossly, and also surrounds every bundle of muscle fibers and each individual muscle cell. This connective tissue is inextricably linked with the muscle, and is continuous with the tendons and periosteum (Figure 1, Figure 2).

The fascia is composed of cells—including fibroblasts, macrophages and mast cells—and extracellular matrix. The extracellular matrix (ECM) is composed of ground substance and collagen and elastin fibers. Fascia is

Fibrosis and adhesions

One of the hallmarks of connective tissue, including fascia, is its mutability and remodeling in response to mechanical stress. However, under certain conditions—excess mechanical stress, inflammation or immobility—this process can result in excessive and disorganized collagen and matrix deposition resulting in fibrosis and adhesions (Langevin, 2008).

In plantar fasciitis and tendinitis of the elbow these types of changes have been reported. Two series of surgical biopsies in patients with

Evidence for fascial dysfunction in fibromyalgia

When Stockman examined muscle biopsy studies of patients with ‘chronic rheumatism’ in 1904, he found inflammatory hyperplasia of the connective tissue. Specifically he described a section of inflamed perimysium which on light microscopic evaluation consisted of a ‘proliferated and oedematous fibrous tissue with an amorphous matrix’, leading him to conclude that ‘the essential pathological changes in chronic rheumatism are confined to white fibrous tissue’ (Stockman, 1904). However, Collins

Growth hormone and sleep abnormalities

Moldofsky was able to cause symptoms of fibromyalgia—widespread muscle pain and fatigue—in healthy patients by depriving them of deep (slow-wave) sleep experimentally (Moldofsky and Scarisbrick, 1976). These symptoms resolved once subject were again allowed deep sleep. Sleep studies have demonstrated that fibromyalgia patients experience reduced deep sleep that is frequently interrupted with alpha-waves which are normally associated with states of wakefulness (Moldofsky et al., 1975).

Growth

Hypothesis

Fascial dysfunction and inflammation may lead to the widespread pain and central sensitization seen in fibromyalgia. This paper proposes that the fascial dysfunction in fibromyalgia could be caused by chronic tension in the fascia and an impaired fascial healing response due to inadequate growth hormone stimulation. In genetically prone individuals, a trauma may trigger prolonged dysfunction of the stress response. This chronic autonomic arousal and hypervigilance may cause excess fascial

Anti-inflammatories in fibromyalgia

If fascial inflammation exists in FM, why are non-steroidal anti-inflammatory medications (NSAID) and corticosteroids ineffective? No improvement in fibromyalgia symptoms was reported with prednisone 15 mg per day for two weeks, or with the NSAID medications ibuprofen and naproxen (Clark et al., 1985, Goldenberg et al., 1986, Yunus et al., 1989b).

This paper argues that there is indeed fascial inflammation in fibromyalgia, but that it is a type of inflammation that is not responsive to oral

Manual therapy in fibromyalgia treatment

In 1904 Stockman recognized the potential of manual therapy in treating chronic rheumatism (what is now called fibromyalgia) and noted that ‘indurated fibrous tissue can however only be removed by local and well-directed manipulations’ (Stockman, 1904). This idea was reiterated recently by a leading fascia researcher, ‘Treatments involving direct mechanical stimulation of connective tissue can potentially reverse connective tissue fibrosis’ (Langevin, 2008). Myofascial fibrotic changes can

Conclusion

This paper presents the hypothesis that fascial dysfunction in fibromyalgia leads to widespread pain and central sensitization. Using other known abnormalities in fibromyalgia, a proposed mechanism leading to fascial dysfunction in fibromyalgia is described.

The in vivo microdialysis techniques developed by Shah's group to assess myofascial trigger points could also be used to evaluate the chemical composition of fascial interstitial fluid for evidence of inflammation (Shah et al., 2005). In

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      The manipulation of fascial layers during reflexology may also have something to add about the alleviation of pain, especially pain associated with inflammation. Cells known as fibroblasts exist in deep fascial structures, which play an essential part in the regulation of inflammation, and the dysregulation of these fibroblasts has been implicated in chronic inflammation [44]. Fibroblasts produce collagen which is a pre-requisite for remodelling and for tissue repair.

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