Access to the PPM Journal and newsletters is FREE for clinicians.
6 Articles in Volume 1, Issue #3
Breaking Down the Barriers of Pain: Part 3
CES: A Practical Protocol for theTreatment of Pain
New Directions
Pharmaceutical Therapies
The Neural Plasticity Model of Fibromyalgia Theory, Assessment, and Treatment: Part 1

The Neural Plasticity Model of Fibromyalgia Theory, Assessment, and Treatment: Part 1

Part one of this series presents the basis for understanding fibromyalgia theories.

New developments in understanding chronic pain, suggest new methods for understanding fibromyalgia. Neural plasticity refers to the way the neurological systems (sensory, motor, and central) react and adapt to the repeated stimulation of chronic pain. Fibromyalgia and fibromyalgia syndrome are presented as an example of this phenomena. Part One of this series presents the basis for understanding fibromyalgia from the neural plasticity model, Part Two discusses assessment procedures, while Part Three develops a comprehensive treatment model.

The term “fibromyalgia” means pain of the muscle and surrounding fibrous tissues of the body. This term has now generally displaced the older term “fibrositis” which was suggestive of an inflammatory or degenerative musculoskeletal disorder. Although still medically classified as a soft tissue rheumatic disorder, as the older term “fibrositis” would imply, fibromyalgia (FM) is more correctly denotative of a generalized, persistent, idiopathic, musculoskeletal pain condition that is associated with the presence of numerous tender points that reliably discriminate this condition from other rheumatic conditions.1

The American College of Rheumatology (ACR) criteria for the diagnosis of FM for research purposes are widespread pain in all four quadrants of the body of at least three months duration and decreased pain threshold. Decreased pain threshold (allodynia) is operationalized by pressure dolorimetry at 18 designated tender point locations and the finding of a minimum 11 of these points as positive for pain at less than 4.0 kg/cm2 of applied pressure.1 FM tender points are displayed throughout the body including the neck, shoulders, chest, back, arms, hips and knees, but the 18 locations designated by the ACR are the most common locations across patients. The use of the ACR 1990 classification criteria for FM provides a sensitivity of 88 percent and a specificity of 81 percent in distinguishing FM from other musculoskeletal pain disorders.1 However, while tender point examination is a clinically reliable technique, 2,3 the presence of many tender points is also associated with depression, fatigue, anxiety, and other somatic symptoms as well as with pain.4,5 Moreover, pain sensitivity and tender point counts will vary as a function of menstrual cycle phase6 and the number of positive tender points less than the prerequisite 11 on early examination fails to predict the later development of fibromyalgia syndrome.7

Although not included as part of the ACR diagnostic criteria, the FM symptom complex also includes a number of other commonly associated symptoms, including sleep disturbances, morning stiffness, fatigue, poor immediate recall, poor concentration, and a decreased ability to multi-task.8,9 Added to the ACR 1990 diagnostic criteria for FM, these additional associated symptoms have come to be designated as “Fibromyalgia Syndrome” (FMS). (Except where otherwise specifically indicated, the term “fibromyalgia” (FM) will be used throughout this paper to designate both the more specific condition of fibromyalgia as well as the broader syndrome itself.)

The identification of FM is further complicated by the fact that it commonly coexists with other conditions and syndromes such as arthritis, chronic fatigue syndrome (CFS), depression and generalized anxiety, headache syndromes, irritable bowel syndrome (IBS), mitral valve prolapse (MVP), primary dysmenorrhea, restless leg syndrome (RLS), systemic lupus erythematous (SLE), temporomandibular joint dysfunction syndrome (TMJ), and myofascial pain syndromes (MPS). 10,11 In particular, FMS and CFS have a great many symptoms in common and a number of studies have shown that a majority of those diagnosed with CFS also meet the ACR 1990 criteria for a diagnosis of FM and, conversely, that more than 50 percent of persons diagnosed with FM also have a current or past diagnosis of CFS.12 Some researchers have pointed out that whether a person gets diagnosed with FMS or CFS is largely dependent on whether they complain more loudly of pain or of fatigue.

Regional soft tissue pain syndromes and FM also share many clinical and psychological features. However, several features, including poor sleep, persistent fatigue, irritable bowel symptoms, bloating, paresthesias, headaches, and number of trigger points are significantly less frequent or fewer in number among persons with regional soft tissue pain than those with fibromyalgia.13

Epidemiological studies have revealed fibromyalgia to be primarily a female disorder, with more than 80 percent of all cases being diagnosed in females14 and prevalent in approximately 2.015 to 3.3 percent16 of the North American population generally. There is also evidence that males with FM experience fewer symptoms and fewer tender points as compared to females with fibromyalgia.17 Although FM is seen in children, it is primarily prevalent between the ages of 40 and 64, with a mean age in the population of approximately 48 years.16 Wolfe15 suggests that many of the elderly population who are diagnosed with arthritis, may actually be suffering from FM, thus increasing the incidence rate for the 60 to 79 age range. Onset appears to be associated with a number of different factors including trauma to the neck,18 low back pain,19 viral infection,20 stress,21 and a combination of these factors. The development of FM has been noted to begin with localized pain in most cases, with a clearly increasing tendency for patients with regional and chronic multi-focal pain to develop chronic widespread pain and FMS.22 FM appears to be a chronic and relatively unchanging condition, with up to 85 percent of those diagnosed with the condition continuing to fulfill the diagnostic criteria after four years23 and an average length of time in pain reported as 78.7 months.20

With the passing of a full decade of extensive research and investigation since the development of the ACR classification criteria, the etiology and consequently the treatment of FM continue to be poorly understood. Moreover, although a very small minority, there are still some “doubting Thomases” that insist that FM is not a real medical condition.24

A number of clinical observations strongly support muscle as the primary origin of FM.25 First, most persons with FM clearly cite muscle as the source of their pain and, while many also describe joint stiffness in the mornings and a “bone-deep” aching, radio imaging of bone and joints is almost invariably normal or any noted abnormalities are of insufficient magnitude to explain the intensity of pain experienced.26 Second, most persons with FM experience increased pain during repetitive muscular activity which eases on cessation. Third, persons with FM are generally tender over focal areas of muscle, usually at musculotendinous junctions and there is an improvement in pain after these focal areas of tenderness are injected with anesthetics.27 Fourth, in the majority of cases, FMS appears to develop from unresolved focal myofascial syndromes.28 Finally, Bengtsson and his colleagues used sequential epidural installations of saline, fentanyl, naloxone, and lidocaine to convincingly demonstrate that there is a peripheral muscle component of FM pain.29

However, while there are numerous clinical observations that point to muscles as the primary origin of FM, the ultimately widespread nature of fibromyalgic pain and the many neurosomatic symptoms that are a recognized feature of FMS strongly argue for some systemic process underlying this condition. Despite clear epidemiological overlap with many rheumatic disorders (e.g., rheumatoid arthritis, lupus)30 extensive investigation of blood markers for systemic rheumatalogical disorder have remained inconclusive.31

Numerous other more or less “systemic” theories as to the etiology and pathophysiology of fibromyalgia abound, including: central neurotransmitter imbalances,32,33 neuroendocrine-immune dysfunction,34-36 thyroid hormone resistance,37,38 stress-related physiological changes,39 psychopathology,40-44 psychosocial factors,45 and sleep disturbance (alpha intrusion).46-48

There is a growing body of evidence suggesting the presence of biochemical abnormalities in the FM etiology. Such suggested imbalances include: a generalized deficiency of serotonin,49 low levels of serum tryptophan and other amino acids,50 increased levels of substance P,51-53 and low serum levels of the insulin-like growth factor IGF-1.54 As well, there is evidence of an enhanced pituitary release of adrenocorticotrophic hormones (ACTH) and a low response of this hormone to neuroendocrine tests.39

Russell55 makes a strong case for elevated levels of substance P (SP) in the cerebrospinal fluid (CSF) of FM patients as the most consistent laboratory finding in neurotransmitter investigations of FM and point out that production of SP can be enhanced by ongoing peripheral pain, elevated CSF nerve growth factor, or CSF dynorphin A, all well documented findings in FM research. Moreover, failure of antinociception could result from low metenkephalin or low serotonin levels, both observed in FM.

Because early or frequent awakening with non-restorative sleep is an almost universal complaint of persons with fibromyalgia8 and early research demonstrated that sleep deprivation in healthy persons can lead to generalized muscle pain,48 disregulation of central sleep-wake mechanisms has been hypothesized by many researchers as a critical factor in the etiology of FM. There are at least six lines of evidence to support the primacy of sleep disregulation in the etiology of FM. First, clinical investigations over the years have consistently shown a strong association between increasing pain and fatigue and poor sleep ratings. Second, a number of studies have demonstrated that persons with FM frequently show changes in their sleep physiology, including presence of an alpha intrusion (7.5-12 Hz) EEG anomaly during sleep, periodic involuntary limb movements, periodic K-alpha EEG, and apnea-hypo apnea occurring during sleep. Third, when the slow wave sleep of healthy persons is disturbed by noise, these people also manifest alpha EEG sleep anomaly, non-restorative sleep, and diffuse myalgia and fatigue. Fourth, persons with FM show measurable diminution in cognitive-performance functions that are susceptible to sleep deprivation. Fifth, unlike those with FM, persons with chronic somatoform pain disorder do not generally complain of non-restorative sleep and do not show alpha EEG sleep anomaly. Sixth, retrospective studies show that the alpha EEG sleep anomaly and symptoms of non-restorative sleep may follow a febrile episode.46-8,56,57

Moldofsky48 suggests that this disruption may be attributable to a disturbance in serotonin metabolism. In addition, a study by Bennett and colleagues54 suggests that a lack of slow wave sleep disrupts the release of GH-1. However, both of these findings have been disputed by other studies19 and thus the delta-alpha sleep disregulation theory remains debatable.

Autonomic nervous system imbalance has also been implicated in the development of FM.58 Using power spectral analysis of heart rate variability, a few researchers59,60 have pointed out that the basal autonomic state of persons with FM is characterized by increased sympathetic and decreased parasympathetic (vagal) tone with associated increased resting heart rate, reduced heart rate variability, and deranged response to orthostatic stress. Quality of life, physical function, anxiety, depression, and perceived stress were found to be moderately to highly correlated with the degree of imbalance between sympathetic and parasympathetic tone. Moreover, there is a high incidence of Raynaud’s syndrome associated with FM.61

FM continues to be defined primarily in terms of the complaint of widespread soft tissue or muscular pain, yet FM is clearly much more than just muscle pain. Moreover, the pervasive eclectic symptomatology of the typical FM sufferer cannot be explained by any one pathophysiological aberration.25

Chronic Benign Pain and Fibromyalgia

Although FM has been generally viewed as a muscle pain disorder and traditionally classified as a non-articular rheumatic disease, it also clearly falls within the area of chronic benign pain as defined by the International Association for the Study of Pain (IASP).62 Chronic benign pain is defined as pain of a non-life threatening nature that lasts for more than six months. After more than a century of failing to adequately explain chronic benign pain in terms of peripheral nervous system (PNS) and/or psychological phenomena, pain researchers are increasingly turning to the neurosciences and investigating chronic pain as a central nervous system (CNS) phenomenon.63-65 The preliminary results of these works indicate that the central nervous system (CNS) (including the dorsal horn and the cortex) may react to persistent pain by becoming sensitized, and that plastic changes in the CNS then increasingly become involved in the maintenance of chronic pain.66 Donaldson21 and Mueller67 applied this thinking to FM, suggesting that FM may involve central as well as peripheral neurological dysfunctions.

The American College of Rheumatology criteria for the diagnosis of FM for research purposes are widespread pain in all four quadrants of the body of at least three months duration and decreased pain threshold.

Wolfe et al.15 in their article on the prevalence of FM in the general population, made the cogent observation that the “association between FM and chronic pain, aging, and musculoskeletal deterioration or arthritis suggests that one possible causal relationship for FM is other musculoskeletal pain.” Supporting this observation, it has been variously noted that for the vast majority of persons with FM their end-state condition was preceded by persistent localized or regional pain.18,28

Certainly, with respect to FM, there is strong evidence that persons with this particular benign chronic pain disorder demonstrate a generalized hypervigilance to both pain and auditory stimuli68 as well as qualitatively altered nociception;69-74 with a reduction in pain threshold (allodynia), an increased response to painful stimuli (hyperalgesia,) and an increase in the duration of pain after nociceptor stimulation (persistent pain) – all findings that support the hypothesis of centralized pain amplification in FM.

Neural Plasticity

There is strong evidence that persistent or chronic noxious stimulation can sensitize both the CNS and PNS structures involved in pain perception.64,75-77 This process of central and peripheral neurosensitization is called neural plasticity and is likely a very important factor in the pain experience of persons with FM as well as in the development of other “traumatic disability syndromes”78 such as post concussion syndrome, post traumatic stress disorder, multiple chemical sensitivity, and chronic pain disorder66 as well as phantom limb sensations and pain.79,80 Neurosensitization or neural plasticity (hereafter referred to as plasticity) refers to changes in reactivity of the nervous system and its components as a result of constant successive activations.81 As a result of repeated exposure to pain stimulation, plasticity may be seen in the process whereby the CNS or the PNS: a) grows in size,76 b) alters the area(s) of innervation,82 or c) becomes more responsive to the pain signal.64 Essentially, plasticity refers to a re-wiring of synaptic connections, which can result in amplification of peripheral inputs, or, if prolonged, a pain state in the complete absence of peripheral input.83

Repeated stimulation of the neural pathways by the pain signal can lead to changes in functioning which have a direct impact upon the maintenance of chronic pain. This may be seen as changes in: a) the peripheral sensory neural pathways, b) the afferent from a muscle spindle fiber as it impacts upon the motor neuron pool, and c) the brain itself.

Peripheral Sensory Neural Pathways

Repeated stimulation of a nerve causes it to grow in diameter and to invade more receptor sites than before (especially if these areas are not receiving neural stimulation),84 potentially affecting a wider area.76 Repeated stimulation of the receptor sites at the dorsal horn leads to changes in receptor sites,63 including both a reduction in their threshold of activation as well as increases in extraneous background neural activity, which may stimulate the now more sensitive receptors.

Finally, research has shown that sensory input from muscle, as opposed to skin, is a much more potent effector of CNS sensitization.1,77,85,86 For example, the pain signal from muscle tissue is larger in amplitude and impacts upon the receptor sites at the dorsal horn for a longer period of time (90 msec) than that of a pain signal from a cut on the skin (15 msec).5 In most traumas (chronic pain situations), when connective tissue is involved, increased pain may be expected.

Muscle Spindle Fiber Afferent

Stretching a muscle upon its length will not only produce tissue damage (tearing of the sarcoma causing leakage of calcium, potassium, and other biochemicals into the surrounding tissue),87 but also alters the afferent generated by the muscle spindle fibers,88 further compounding the problem. The type of contraction that the muscle is undergoing immediately before the stretch determines the manner in which the afferent is altered.89 If the muscle is in an eccentric (lengthened) position, the afferent generated immediately after will be decreased, whereas if the muscle is in a concentric (shortened) position the subsequent afferent will be increased. This is why knowledge of the positioning of the person at the moment of trauma is so important in understanding the resulting muscle injury and dysfunction. For example, if a person is in a rotated position (i.e., head turned to the left) one muscle out of the homogeneous pair must lengthen while its contralateral partner must shorten for rotation to occur. If the insult is recent (within six weeks) the experienced pain most likely involves inflammation.90 However, if the pain persists beyond six weeks it probably involves taut bands and trigger points87 that may be located within the injured muscle itself or in other muscles of the same mitotic unit. As the timeline increases, it is reasonable to expect more involvement with trigger points and less from inflammatory processes. Surface electromyography (sEMG) can be used after the swelling has gone down to document the changes in afferent and direct neuromuscular retraining (see Part Two; section on Assessment).

As the length of time post injury increases, it can be expected that the number of trigger points will also increase due to the development of secondary or satellite trigger points. Whether this is due to a change in the biomechanical aspects of the muscle activity about the joint (see below) or alterations in the neural pathways (see below) or a combination of these factors is not clear. Also it is not entirely clear why trigger points spread more rapidly in one person versus another, although stress-related physiological differences and genetic factors are suspected.


It is only recently that researchers have started to examine the impact of chronic pain upon the brain. While many health care practitioners regard the brain as a passive recipient of the pain signal, current research91 suggests that the brain is very much involved in the perception of pain and reacts to constant stimulation by the pain.63,92,93 This reaction is just starting to be understood.94 In the dorsal horn, repeated stimulation appears to sensitize the CNS, requiring less stimulation for reaction and creating more intensity in that reaction.85 In addition, the neural plasticity model suggests the brain’s reaction may become independent of the peripheral pathology as seen in the development of phantom limb pain. This latter phenomenon has been demonstrated and reported by various authors such as Coderre64 and Birbaumer.63

The evidence for changes in brain functioning as a result of repeated noxious stimulation is quite persuasive.94 With respect to FM, a number of researchers have reported findings supporting an association with changes in brain functioning. For example, persons with FM have been shown to produce amplified cerebral evoked potentials as compared to normal in response to noxious heat stimulation95 and FM patients characterized by lower pain thresholds show decreased regional blood flow in the thalamus and caudate nucleus compared to normal controls.96 Flor-Henry97 has found characteristic EEG abnormalities involving the power distribution of theta (4-7 Hz) and high beta (20-50 Hz) brain waves in persons with FM as compared to normal. Similarly, Donaldson21 reported that the EEG power distribution of the brain, particularly in the frontal cortex changes in FM patients, and improvement in symptoms was correlated with changes in this power distribution (discussed in detail later).

Compared to healthy individuals, patients with FM are characterized by significantly lower resting state levels of regional cerebral blood flow in the thalamus and caudate nucleus.96,98 Moreover, insidious onset of FM is associated with significantly lower rCBF than normal controls in the left and right caudate nucleus as well as the left and right thalamus, whereas traumatic onset of FMS is associated with significantly lower rCBF than normal controls in the left and right thalamus only.99 These differences between insidious onset and traumatic onset FM groups were not associated with any variations in behavioral or physiological measures of pain processing (i.e. pain threshold, clinical pain intensity, or CSF levels of sP). This research suggests that regardless of type of symptom onset, central sensitization is the final common pathway for the development of abnormal pain perception in persons with FMS.


Evidence indicates that the nervous system is dramatically altered by persistent injury and by noxious inputs produced by the injury.94 Coderre goes on to state “ in some cases peripheral tissue damage or nerve injury leads to a pathological state characterized by one or more of the following: pain in the absence of a noxious stimulus, increased duration of response to brief stimulation, reduced pain threshold, increased responsiveness to suprathreshold stimulation, and spread of pain and hyperalgesia to uninjured tissue” 64

Thus, it is believed that as with all neural systems, the more the system is stimulated, the more efficient it becomes and the more easily it is stimulated; in the end requiring ever less intense and fewer stimuli to cause more pain.

Read Part 2 of this article series

Last updated on: January 6, 2012
close X