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Hypothesis: The Chaos and Complexity Theory May Helpour Understanding of Fibromyalgia and Similar Maladies

Manuel Martinez-Lavin, MD, Oscar Infante, DVM,and Claudia Lerma, PhD

Background:Modern clinicians are often frustrated by their inability to understand fibromyalgiaand similar maladies since these illnesses cannot be explained by the prevailing linear-reductionistmedical paradigm.

Objective:This article proposes that new concepts derived from the Complexity Theory may helpunderstand the pathogenesis of fibromyalgia, chronic fatigue syndrome, and Gulf War syndrome.

Methods:This hypothesis is based on the recent recognition of chaos fractals and complex systemsin human physiology.

Results:These nonlinear dynamics concepts offer a different perspective to the notion of ho-meostasis and disease. They propose that the essence of disease is dysfunction and not structural

damage. Studies using novel nonlinear instruments have shown that fibromyalgia and similarmaladies may be caused by the degraded performance of our main complex adaptive system. Thisdysfunction explains the multifaceted manifestations of these entities.

Conclusions:To understand and alleviate the suffering associated with these complex illnesses, aparadigm shift from reductionism to holism based on the Complexity Theory is suggested. Thisshift perceives health as resilient adaptation and some chronic illnesses as rigid dysfunction. 2007 Elsevier Inc. All rights reserved. Semin Arthritis Rheum xx:xxxKeywords:fibromyalgia, chronic fatigue syndrome, chaos, Complexity Theory, irritable bowel, Gulf War syndrome, neuropathic pain, complex adaptive systems, autonomic nervous system

The whole is more than the sum of its partsAristotle

Modern clinicians are often frustrated by theirinability to understand common complex syn-dromes such as fibromyalgia (FM) and similar

maladies because such illnesses cannot be properly ex-plained through the prevailing linear-reductionist medi-cal paradigm. This poor understanding often severs thepatientphysician relationship and consequently resultsin persistent patient suffering and dissatisfaction.

This article proposes that new paradigms derived fromthe Complexity Theory may help us better understand

these multifaceted syndromes. The focus of the proposalis on FM, but the hypothesis may be also relevant torelated overlapping conditions such as the chronic fa-tigue, Gulf War, and irritable bowel syndromes. The hy-pothesis is based on the recent recognition of chaos frac-

tals and complex systems in human physiology (1,2).These nonlinear dynamics concepts offer a different per-spective to the notion of health and disease. Studies usingnonlinear methods have suggested that FM and similarmaladies may be caused by the degraded performance ofour complex adaptive systems (3).

METHODS

New concepts derived from the Complexity Theory arereviewed. Based on this theory, a new perspective on FMis offered.

RESULTS

The Complexity Theory

Scientists frequently view the universe as a linear place,one where the simple rules of cause and effect apply,and where the strength of the response is proportionateto the magnitude of the stimuli. This is analogous tothe way one studies a big machine and takes it apart tounderstand its components, and in that manner, un-derstands the whole. However, after the introduction

National Institute of Cardiology, Mexico City, Mexico.

Address reprint requests to Manuel Martinez-Lavin, MD, National Institute of

Cardiology, Juan Badiano 1, 14080 Mexico City, Mexico. E-mail: mmlavin@

infosel.net.mx.

10049-0172/07/$-see front matter 2007 Elsevier Inc. All rights reserved.doi:10.1016/j.semarthrit.2007.04.003

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of computer modeling and simulation, it became clearthat the universe is full of systems that do not followthis linear behavior. In such networks, proportionalitydoes not hold, and small changes can have striking andunanticipated chaotic effects. These systems cannotbe understood by analyzing their individual compo-nents (1,2). As scientists of all disciplines exploredthese phenomena, a new field of study emerged, The

Complexity Theory, which is based on relationships,emergence, patterns, and iterations. The roots of thistheory are found in Poincars restricted 3-body prob-lem in the early twentieth century (4) and on thecybernetic model developed by Wiener and Rosenblu-eth (5).

As a consequence of this emerging knowledge, novelconcepts appeared. Some of them are essential to compre-hend this hypothesis (1,2).

Complex systems are macroscopic collections of simple(and often nonlinearly) interacting units that are en-dowed with the ability to evolve and adapt to a changing

environment. The control of a complex system tends to behighly dispersed and decentralized with negative (damp-ing) and positive (amplifying) feedback loops. Thesefeatures provide resilience in the face of environmentalperturbation, thus the term complex adaptive systems.Examples of complex systems are democratic societies,stock markets, ant colonies, the immune system, and theautonomic nervous system (ANS).

Emergenceis the process of complex pattern formationfrom more basic constituent parts or behaviors. An exam-ple is the interactions between a great number of neuronsproducing a human brain capable of thought. The con-

stituent neurons are not individually capable of thought.Emergent structures are more than the sum of their partsbecause the emergent order will not arise if the variousparts are simply coexisting; the interaction of these parts iscentral.

Chaosrefers to apparently random unpredictable vari-ability that can arise from the operation of complex sys-tems. The unpredictability comes from a property knownas sensitivity to initial conditions, which means thatsmall changes or perturbations can produce large trans-formations in the behavior of the system in the long term(the butterfly effect). Chaotic systems can also have bi-furcations (sudden changes in behavior in response to

small change in 1 parameter or property of the system).Chaotic behavior can be seen in different networks of thehuman body such the nervous or immune systems.

Fractalis a geometric concept related to chaos. A fractalis an object composed of subunits that resemble the largerscale structure, a property known as self-similarity.Most important human structures have fractal anatomies.Perhaps the best example is the pulmonary circulation.The pulmonary artery branches thousands of times beforereaching the capillary bed. The microscopic pulmonarysubunits and its larger counterparts are shaped identically.Fractal structures are extremely efficient for transporta-

tion, distribution, and exchange. Fractal also has a timedomain concept that is applied to complex processes lack-ing a single time scale (1,2).

DISCUSSION

The Concept of Disease: Time to Amendthe Paradigm

The prevailing paradigm considers medicine to be a linearscientific discipline. It views the human body as a bigmachine that can be understood by carefully examiningits parts. This reductionist approach has been useful inunderstanding many linear diseases. The cause effectof an infection or a tumor causing organ damage led to thevery useful clinicalpathologic correlation. Such educa-tional exercises are still the main event in many medicalcenters and medical journals. Therefore, current scientificthinking demands that a true disease must have struc-tural (or at least serological) alteration. According to thisview, if a clinical syndrome (the effect) does not have an

underlying anatomic alteration (the cause), then eitherthe syndrome is nonexistent or the illness belongs to therealm of psychiatry. This sophism derives in part fromRene Descartes philosophy that distinguished betweenres cogitansand res extensa. The former referred to the soulor mind and was said to be essentially a thing whichthinks. The latter was the material stuff of the body. Itsprimary characteristic was extension: it occupied spaceand was therefore amenable to measurement (6).

An alternative view envisioned by Claude Bernard inthe nineteenth century, and supported by the ComplexityTheory, is to define disease as dysfunction. Structuraldamage without dysfunction is not disease. Dysfunction

with or without structural damage is disease. Thus diseasecan be broadly defined as a bio-psycho-social alterationthat generates suffering (7) and/or decreases longevity.

Disorder Is Healthy, Uniformity Leadsto Disease

Conventional medical wisdom contends that diseasesarise from deviances of the orderly machine-like systemsof the body. The Complexity Theory challenges this view,suggesting instead that the opposite is true (2). A systemin idle equilibrium does not have the internal dynamicsenabling it to respond to its environment and will ulti-

mately die. A system in deterministic chaos may haveresilience in the face of external stressors. A good exampleof healthy chaotic behavior is the constant variation of theheart beat (8).

In normal circumstances, the heart rate is not fixed,rather it varies constantly in a seemingly random way,particularly during resting conditions. Irregularity of theheart beats follows a circadian rhythm with increased beatdispersion during sleep (9).

Analyses of the variability of heart rate, looking at tra- jectories in the space, and self-similarity properties haverevealed chaotic behavior (9,10).

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Healthy individuals have widely varying heart beats. Inthe presence of disease or aging, the system loses complex-ity and this variability decreases (9). In elderly persons,altered fractal scaling properties of heart rate are a predic-tor of sudden death (11).

The Autonomic Nervous System, a Prototype

of a Complex Adaptive SystemThe ANS is an intricate network in vertebrate animalsthat serves to regulate the most important body functions,including the vital signs. The term autonomic reflectsthe fact that the system is not governed. Blood pressureand heart rate (among many other variables) are finelytuned by harmonious sympatheticparasympathetic in-teractions that take place through internal feedback paths.These 2 branches act as amplifying or damping feedbackloops constantly adapting the body to environmentalchanges.

The ANS is the interface between mind and body.

Autonomic activation transforms emotions like fear oranger into biological functions like paleness, pupil dila-tion, and tachycardia, among many other reactions.Therefore this network constitutes the main element ofthe stress response system (12). The ANS has all the fea-tures of a complex adaptive system.

The performance of this complex adaptive system isvery difficult to assess. Static blood or urine measurementsof autonomic neurotransmitters do not reflect the dy-namic nature of the ANS. The introduction of a nonlinearinstrument (heart rate variability analysis) made it possi-ble to follow and estimate the chaotic behavior of this

network (9,10).Heart rate variability is under the control of the ANS.Variations in heart period are largely dependent on vagalmodulation. Spectral methodology applied to this vari-ability is capable of defining and quantifying sympatheticand parasympathetic influences on the sinus node (13).

The Fibromyalgia Problem

FM is a chronic syndrome characterized by widespreadpain and widespread allodynia. Other distinctive featuresare paresthesias, sleep disturbances, chronic fatigue, anx-iety, and irritable bowel (14). The syndrome affects be-

tween 2 and 3% of the general population, the over-whelming majority (90%) being women. FM severelydiminishes the quality of life of the afflicted persons (15)and imposes a high economic burden on the society (16).Therefore the condition represents a major health prob-lem for contemporary women.

FM strongly overlaps with other prevalent (and contro-versial) clinical conditions such as the chronic fatigue andGulf War syndromes. Common to these illnesses is thepresence of chronic nonnociceptive pain, unexplainablefatigue, sleep disorders, cognitive impairment, anxiety,and depression (17,18). Irritable bowel and temporoman-

dibular joint syndrome are, in many instances, localizedexpressions of the above-mentioned maladies.

There are no consistent anatomical or serological ab-normalities in FM and similar syndromes. This lack ofstructural damage led some clinicians to argue that theillnesses were nonexistent. Nevertheless, it is an undis-puted fact that physicians are often consulted by personscomplaining of vexing pain and fatigue that cannot be

explained by any other diagnosis.

Autonomic Decomplexification inFibromyalgia and Related Illnesses

Different groups of investigators have reported decreasedheart rate variability in patients with FM, as well as amonotonous circadian rhythm pattern (2,19-25). Thesefindings are the most consistent alterations so far de-scribed in FM. These anomalies can be interpreted as adecomplexification of the ANS, with persistent inflexi-ble circadian sympathetic predominance. Similar heart

rate abnormalities have been reported in conditions thatoverlap with FM such as irritable bowel (26,27), chronicfatigue (28), and Gulf War syndrome (22,29).

It has been suggested that such autonomic dysfunctionexplains the multifaceted alterations in FM (30) and thatthe main complaint of the syndrome (chronic pain) issympathetically maintained. Emerging evidence suggeststhat the unbending sympathetic hyperactivity could leadto neuroplasticity, establishing abnormal connections be-tween the sensory neurons and the sympathetic nervoussystem. This type of neuroplasticity is a well-establishedphenomenon in the animal model (31). The hormonal-

influenced difference in the behavior of the ANS inwomen versus men (32) could theoretically explain themarked gender difference in the prevalence of FM.

New genomic data reinforce the proposal of FM assympathetically maintained pain. Catecholamines are thesympathetic neurotransmitters. Healthy women withparticular gene polymorphism associated with defectivecatecholamine clearing enzymes have increased suscepti-bility to pain (33).

The mechanisms whereby a breakdown of the ANSmay produce other distinctive FM manifestations havebeen discussed previously (30).

This new information suggests that in FM and related

conditions there is degraded performance of the bodysmain complex adaptive system, the ANS. The reason forthis decomposition remains to be established. It is possi-bly a combination of environmental and genetic factors.Modern societies have become more stressed (12); theyconfront a more hostile environment. An example of thenew challenges are alterations in circadian rhythmicity.For thousands of years, day and night cycles were harmo-nious with external cues. Light, noise, and activity duringthe day; darkness, rest, and quiet at night. Industrializa-tion has clearly disturbed this harmony. Nowadays thereis light, activity, and noise at night. Another example of

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modern stressful situations can be seen in monotonousworking conditions. It has been shown that disability inFM is associated with repetitive manual tasks, low in-come, or inability of affected persons to influence their

working environment (34). These and many other stres-sors of modern societies are likely to have a negative im-pact on human health. Individuals that are more suscep-tible to environmental changes (arguably women with

defective catecholamine-clearing enzymes) would,thereby, be more prone to become ill.

Failed Reductionist Therapies forFibromyalgia

Therapy for FM and related illnesses has followed a linear-reductionist paradigm. Conventional physicianpatientinteraction usually results in tests seeking to probe each ofthe patients symptoms. The information derived fromthese series of tests is typically nonrevealing. Nevertheless,physicians will write a prescription for several drugs in-

tended to improve each one of the patients symptoms.The results are often frustrating. Symptoms may not im-prove and patients will often end up polymedicated withadditional suffering caused by the untoward effects of thedrugs.

Interventions that have proven to be partly effective inthese complex syndromes are those multidisciplinary pro-grams that consider a person as a whole, specifically, ed-ucation, cognitive behavioral therapy, and several types ofexercise programs (35,36). These interventions improvethe resting autonomic tone (37).

It is clear that current therapies for FM and related

illnesses are far from adequate. There is much to belearned about the pathogenesis of these syndromes to of-fer more coherent therapy. Meanwhile it seems reasonableto use a scientifically holistic approach including educa-tion, mindbody interventions, and the judicious use ofmedications. These interventions can be better deliveredin clinics specifically designed for this purpose (36).

In conclusion, FM and similar maladies are clinicalrealities. Attitudes such as denial, scorn, or rejection areunacceptable in a scientifichumanistic medical environ-ment. Reductionist approaches have failed to compre-hend these illnesses. These chronic syndromes could bebetter understood on a bio-psycho-social context rather

than attempting to explain such diverse symptoms by thepresence of discrete anatomical or serological alterations.The use of nonlinear instruments based on the Complex-ity Theory has revealed degraded complex adaptive sys-tems in FM and related syndromes. Faulty performanceof the ANS provides a coherent explanation for the mul-tifaceted manifestations of these maladies.

Understanding these syndromes calls for a shift in par-adigms, from reductionism to holism based on the Com-plexity Theory. This shift would recognize chaos, fractals,and complex systems as essentialelements in human phys-iology and would offer a different perspective in which

health is perceived as resilient adaptation, and somechronic illnesses are perceived as rigid dysfunction.

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