Introduction
It is classically thought that inflammation secondary to tissue damage (i.e. trauma, infection or autoimmune disorder) is necessary for the production of fibrous adhesion. These pathways are well understood and available in many texts on the subject. However, mounting evidence suggests there may be an additional pathway to fibrous adhesion production.
A close examination of recent scientific and clinical evidence supports the hypothesis that fibrous adhesion can be produced in the absence of inflammation. This pathway is possible via hypoxic mechanisms.
What is a fibrous adhesion?
Fibrous adhesion is mass of connective tissue matrix consisting of primarily collagen and fibrin. The term adhesion is derived from the process of uniting two surfaces or parts. Scar tissue is a specific type of fibrous adhesion that fills a tissue gap created by cell death or trauma. Therefore, scar tissue implies a traumatic mechanism of production where adhesion does not. The term fibrous adhesion will be used thorough this paper as it is more encompassing.
Hypoxic Fibrous Adhesion Pathway
There are four critical steps in the hypoxic production of fibrous adhesion.
1. Repeated or sustained contraction of skeletal muscle results in decreased intracellular oxygen concentrations.
2. Decreased oxygen concentrations leads to the production of oxygen free radicals.
3. Oxygen free radicals are very fast, specific and sensitive triggers for attraction and replication of fibroblasts.
4. Increasing fibroblast density leads to increased collagen production and other ultrastructural changes forming fibrous adhesion.
Howlett et al1 demonstrated in single skeletal muscle fibers that the rate of fall in intracellular oxygen concentration is dependent on contraction frequency. Increasing contraction frequency resulted in progressively larger drops in oxygen concentration. In a similar study Kindig et al2 demonstrated that longer contraction duration also resulted in decreased oxygen concentrations.
Fletcher et al3 determined that hypoxia triggers the production of oxygen free radicals which cause normal peritoneal fibroblasts to produce fibrous adhesion. Exposure of fibroblasts to hypoxia resulted in an irreversible increase in TGF-B1 and type I collagen. This reaction could be prevented by adding free radical scavengers. Their findings support the link between hypoxia, free radical production and the development of adhesion.
Other researchers have further demonstrated the relationship between low oxygen levels and the proliferation of fibroblasts4 as well as oxygen free radicals providing a very fast, specific and sensitive trigger for fibroblast proliferation5. It has even been demonstrated that fibroblasts themselves release oxygen free radicals, potentially creating positive feedback for further increasing fibroblast density.
Murrell et al. confirmed that increased cell density of fibroblasts is the critical factor in fibrotic conditions that leads to fibrous adhesion6.
Further support of the dual pathway to fibrous adhesion production is seen in cases of radiation toxicity. Radiation has long been used to destroy tumors. However, the radiation also damages healthy tissue. Of particular interest is microvascular injury that leads to an early inflammatory process and a delayed (3-12 month) fibroproliferative process7. Free radical production secondary to radiation treatment has been implicated in causing muscular fibrosis8.
Clinical Importance
Understanding of the hypoxic fibrous adhesion pathway should encourage clinicians to see musculoskeletal disorders in a new light. The presence of fibrous adhesion should be considered in any MS disorder that involves sustained or repeated muscular contraction.
Poor or prolonged postures, repetitive motions and athletic pursuits can cause fibrous adhesions to be produced in the absence of inflammation, trauma or surgery.
Many conditions exist (mensciod entrapment, disc derangement, altered axis of rotation etc.) that cause protective muscular hypertonicity. Hypertonicity is a state of sustained contraction that could, over time, trigger the hypoxic fibrous adhesion pathway. Fibrous adhesion would then be an additional pathology to address with specific treatment tactics.
Diagnosis of Fibrous Adhesion
Surgeons often report visualizing fibrous adhesions during surgical procedures. As a diagnostic method this is reliable but highly invasive. Diagnostic ultrasound can be used to diagnose the presence of fibrous adhesions. This is non-invasive and has the added benefit of visualizing motion as well. The drawbacks to diagnostic ultrasound include sensitivity (large areas of fibrous adhesion are necessary to discriminate from healthy tissue) and expense. Adhesions can be identified by limited ranges of motion. Of course this is non-specific to adhesion and therefore best used as pre and post treatment assessment combined with other techniques. Skilled palpation is extremely useful in identifying fibrous adhesion9. The only possible difficulty with palpation is that it requires significant skill to be reliable (we recommend the Integrative Diagnosis methods for diagnosis of adhesion). Instrument assisted palpation can be helpful in certain tissues as well.
Conclusion
Fibrous adhesions can be produced via hypoxic mechanisms without trauma or inflammation.
Since fibrous adhesion can develop from sustained or repeated muscle contraction they may occur as frequently as other common MS disorders such as weakness and joint dysfunction. Therefore, fibrous adhesion should be considered in the diagnostic workup of most MS complaints. For long term effectiveness treatment tactics must be geared directly toward the reduction of adhesion.
Note: This is a brief clinical review, not an exhaustive literature review. There is a lot of good research to support these claims not cited here. I welcome your thoughts and comments.
William Brady, DC, CSCS
Integrativediagnosis.com
ManualAdhesionRelease.com
References:
1. Howlett RA et al. Intracellular PO2 kinetics at different contraction frequencies in Xenopus single skeletal muscle fibers. J Appl Physiol. 2007 Apr;102(4):1456-61.
2. Kindig CA et al. Effect of contractile duration on intercellular PO2 kinetics in Xenopus single skeletal myocytes. J Appl Physiol.2005 May;98(5):1639-45.
3. Fletcher NM et al. Hypoxia-generated superoxide induces the development of the adhesion phenotype. Free Radic Biol Med. 2008 August 15; 45(4): 530–536.
4. Falanga V et al. Low oxygen stimulates proliferation of fibroblasts seeded as single cells. J Cell Physiol. 1993 Mar;154(3):506-10
5. Murrell GC et al. Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 1990;265:659-665.
6. Murrell GC et al. Dupuytren’s contracture. Fine structure in relation to aetiology. J Bone Joint Surg Br. 1989 May;71(3):367-73.
7. Wang J et al. Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy. World J Gastroenterol. 2007 Jun 14;13(22):3047-55.
8. Wegrowski J et al. (1987)in The Control of Tissue Damage, vol. 2, pp. 39-42, Elsiver, Amsterdam.
9. Leahy PM. (1996) in Active Release Techniques, pp.21-29, Aactive Release Techniques LLC, Colorado Springs CO.