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11 Articles in Volume 16, Issue #7
A Perspective on Tapentadol Therapy
Acupuncture to Treat Brachial Plexopathy and CRPS
Behavioral Medicine: How to Incorporate Into Pain Management
EpiPens and Opioids: Common Ground
Fibromyalgia and Coexisting Chronic Pain Syndromes
Life-Saving Naloxone: Review of Currently Approved Products
Medical Foods Hold Promise In Chronic Pain Patients
Moving Beyond Pain Scales: Building Better Assessment Tools for Today’s Pain Practitioner
Moving Toward an (Almost) Opioid-Free Emergency Department
No Perfect Medicine—What You Need to Know About NSAIDs and Opioids
Prescribing Opioids: How New Policies Are Affecting Medical Specialties

Fibromyalgia and Coexisting Chronic Pain Syndromes

Having 1 central sensitization syndrome places the patient at higher risk of developing another syndrome. Learn more about their overlapping symptoms, effects on the brain, and management.

Fibromyalgia is associated with many somatic symptoms, including fatigue, gastrointestinal complaints, and headaches. Five physical and psychological symptoms, called the SPADE pentad—sleep disturbance, pain, anxiety, depression, and low energy/fatigue—have been especially prominent in subjects with other chronic pain conditions, making the differential diagnosis sometimes difficult.1

Indeed, there is a significant overlap between fibromyalgia and what have been termed the functional pain disorders: irritable bowel syndrome (IBS), interstitial cystitis/painful bladder syndrome (IC/PBS), vulvodynia, migraine, and temporomandibular joint disorder (TMJD), also termed orofacial pain. These disorders all are now considered on the spectrum of central sensitization syndromes.2

The overlap of symptoms among these syndromes was illustrated in a survey of 2,299 people living in northwest England. Of the almost 2,300 participants, 27% (587 people) reported having 1 or more syndrome, including chronic widespread pain (CWP), orofacial pain, IBS, or chronic fatigue. Of the 587 patients, 404 (18%) had 1 syndrome, 134 patients (6%) reported 2 coexisting conditions, 34 patients (2%) reported 3, and 15 patients (1%) had all 4 syndromes (Table 1).2

Having 1 central sensitization syndrome places the patient at higher risk of developing another syndrome,3 including chronic fatigue syndrome (CFS) and chronic headache. The odds ratio for comorbidity of fibromyalgia, chronic headaches, IBS, TMJD, and IC/PBS has varied from 3 to 20 in twin studies and in large population database surveys.4 In addition, the number of pre-existing functional somatic syndromes was noted to be a strong risk factor for the presence of fibromyalgia, CFS, and IBS.5

This review will examine the relationship between fibromyalgia and IBS, IC/PBS, vulvodynia, migraine, and TMJD.

Making the Diagnosis

The exact label of a central sensitization syndrome may depend on the type of specialist the patient sees rather than on substantial clinical differences between these common disorders.6

A Central Sensitization Inventory (CSI) was proposed as a new self-report screening instrument to help identify patients with these overlapping syndromes, including fibromyalgia.7 In a study evaluating CSI, approximately 75% of the subjects met clinical criteria for 1 or more central sensitization syndromes, and “CSI scores were positively correlated with the number of diagnosed central sensitization syndromes.”7

Irritable Bowel Syndrome

IBS has been reported to occur in 7% to 21% of the general population.8 Part of the reason there is such a wide variation in reported prevalence is the different diagnostic criteria that have been proposed. According to Chey et al, “Factors important to the development of IBS include alterations in the gut microbiome, intestinal permeability, gut immune function, motility, visceral sensation, brain-gut interactions, and psychosocial status.”8

IBS is subdivided into 3 categories: IBS with diarrhea, IBS with constipation, or mixed IBS. Symptoms of IBS are similar to those of fibromyalgia and the other central sensitization disorders, including heightened pain sensitivity, excess fatigue, and sleep and mood disturbances.9-14

In addition to overlapping symptoms, IBS and fibromyalgia frequently coexist. The prevalence of IBS in patients with fibromyalgia has varied from 30% to 70%, according to a number of studies.8-12 In 1 study from Norway, the prevalence of IBS was found to be 8.4%, with women affected more often than men.13 Patients with IBS are also at higher risk of having fibromyalgia (OR = 3.6), as well as patients with mood disorders (OR = 3.3). The co-
occurrence of IBS and fibromyalgia is more common in women than in men, and many patients with IBS also suffer from chronic fatigue.9

As noted, generalized pain hypersensitivity is a characteristic of IBS.14 This has been demonstrated in adults, adolescents, and children with IBS.14,15 In a population-based study, adolescents with IBS had a higher incidence of hyperalgesia (lower heat-pain thresholds and pressure-pain threshold) compared with controls—suggesting a central sensitization process in patients with IBS.15

Magnetic resonance imaging studies of patients with IBS have demonstrated strikingly similar pathophysiologic findings to those found in patients with fibromyalgia.16-23 For example, patients with IBS who were found to be excessively sensitive to painful stimuli had greater activation of the insula and reduced deactivation in the pregenual anterior cingulate cortex during noxious rectal distensions, compared with controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in the right hippocampus than controls.17 Imaging studies also found that IBS patients had “lower fractional anisotropy (FA) in the thalamus, the basal ganglia, and sensory/motor association/integration regions, and higher FA in the frontal lobe and the corpus callosum.”21 These imaging studies demonstrating altered pain sensitivity are found more frequently in women with IBS.

A study of women also found increased pain sensitivity and heart rate variability (fight-or-flight response) in patients with fibromyalgia or IBS, compared with controls. In the study, a cold water immersion test found that pain intensity scores were highest in fibromyalgia, intermediate in IBS, and lowest in controls.18 Furthermore, the researchers found that the fibromyalgia patients had the greatest parasympathetic activity based on heart rate variability analyses. The increased pain sensitivity seen among women and adolescents with IBS may be due the duration of severe chronic abdominal pain.19,20

Women with IBS also reported decreased pain inhibition, as well as increased incidence of anxiety, pain catastrophizing, and depressive symptoms.23 The authors concluded that IBS patients had a thicker right posterior insula, which correlated with longer duration of disease. Another study suggested that the alterations in brain activity, particularly in the medial prefrontal cortex, could be related to greater mood disturbances in patients with IBS than healthy controls.24 Furthermore, compared to healthy controls, IBS patients had lower brain volumes in the bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen.25 These findings suggest that regions of primary and secondary hyperalgesia are dependent on the primary pain complaint, in this case IBS.24,26-29

Interstitial Cystitis/Painful Bladder Syndrome

IC/PBS is a chronic condition that is characterized by suprapubic pain and urinary symptoms, such as urgency, nocturia, and urinary frequency.30 The IC/PBS patients frequently meet the diagnostic criteria of the other central sensitization syndromes, especially fibromyalgia, CWP, and IBS. In 1 study, 50% of patients diagnosed with IC/PBS also had another central sensitization syndrome.31

Pain threshold testing also found that hyperalgesia (low pain tolerance) was common among IC/PBS patients.32-34 This was especially true when mechanical pressure was applied to the suprapubic area.35 Patients with IC/PBS can be divided into subgroups: those with pelvic pain only and those with pelvic pain and other pain. “Patients identified with pelvic pain and other pain reported more sensory-type pain, poorer physical quality of life, greater somatic depression, poorer physical quality of life, and greater sleep disturbance than those categorized as pelvic pain only,” noted the researchers.36

Brain imaging studies of IC/PBS patients found altered frequency distributions in viscerosensory (post insula), somatosensory (postcentral gyrus), and motor regions (anterior paracentral lobule, and medial and ventral supplementary motor areas) compared to controls.37 In addition, “the anterior paracentral lobule, and medial and ventral supplementary motor areas showed increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in those patients who reported greater pain during bladder filling,” noted the authors.37

In a study comparing brain images of patients with IC to those of healthy controls, the researchers reported increased gray matter volume in several brain regions, “including the right primary somatosensory cortex, the superior parietal lobule bilaterally, and the right supplementary motor area.”37 Often certain regions of the brain of patients with pain have increased gray matter, whereas other areas will have loss of gray matter—it will depend on the type of patient and condition. In addition, researchers have found that women with IC/PBS showed numerous white matter abnormalities that correlated with levels of pain severity, urinary symptoms, and impaired quality of life.38

Primary Headaches

Hyperalgesia (increased pain sensitivity) is a hallmark of both fibromyalgia and patients with chronic migraines.39 Like other chronic pain conditions, fibromyalgia and headaches often co-exist—but the prevalence of migraine in fibromyalgia patients varies considerably between studies. According to 1 study, migraine was present in more than 50% of fibromyalgia patients,40 while other studies reported a prevalence of over 30%.41,42 In a study of 100 fibromyalgia patients, migraine alone was found in 32 patients (32%), including 15 with and 17 without aura, 18 patients with tension-type headache, and 16 with combined migraine and tension-type headache.39

The comorbidity of fibromyalgia and headaches was equally distributed in migraine patients with and without aura. The presence of fibromyalgia was associated with the severity of migraine headaches, as well as with anxiety.40 It is common for patients with chronic headaches to experience widespread allodynia.43 To study the prevalence of cutaneous allodynia, researchers looked at a variety of headache types. They found that allodynia varied with headache type, and was highest in patients with transformed migraine (increasing in frequency over time [Table 2]).43 In the patients with migraine, moderate to severe cutaneous allodynia increased with the frequency of headaches. Increased body mass index also  was associated with increase prevalence of cutaneous allodynia. “In all patients groups, the allodynia scores were higher in subjects with major depression,” noted the investigators

It is known that migraine is frequently found in patients with fibromyalgia, but what is the prevalence of fibromyalgia in migraine patients? A large headache clinic in Italy studied just that question. Of a total of  1,123 primary headache patients screened, fibromyalgia was found in 35% of the tension-type headache group, and in 44% of the chronic tension-type headache subtype.44 The authors noted that the presence of fibromyalgia correlated with “headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability.”

Imaging studies have also shown brain changes related to chronic pain. In 1 study, migraine patients (as compared to healthy controls) had a significant decrease of gray matter in areas traceable to the transmission of pain (cingulate cortex), but not in areas specific for migraine, such as the brainstem.45 In another study, patients with migraine had significant “focal gray matter reduction in the right superior temporal gyrus, right inferior frontal gyrus, and left precentral gyrus.”46 In addition, the researchers in the latter study were able to correlate loss of gray matter in the anterior cingulate cortex with frequency of migraine attacks.42 In subjects with cluster headaches, regional gray matter changes were found in the temporal lobe, the hippocampus, the insular cortex, and the cerebellum.47 “The extent, location, and direction of observed gray matter alterations correlated with headache activity,” noted the authors.

Reviews of functional MRI studies in migraine have demonstrated atypical brain responses to sensory stimuli as well as altered functional connectivity of sensory processing regions.48 The diagnosis and management of coexisting migraine should be taken into account in the assessment and management of fibromyalgia, particularly when headaches are severe or patients suffer from widespread musculoskeletal pain.

Vulvodynia

Vulvodynia has been estimated to occur in between 7% and 8% of women by age 40.49 Vulvodynia and chronic pelvic pain have also been associated with fibromyalgia.50-52 In a population-based study in Minnesota, researchers examined the prevalence of vulvodynia and other central sensitization syndromes. Of 1,890 women screened, the odds ratio of vulvodynia occurring with fibromyalgia was 3.84. The prevalence of IC, vulvodynia, IBS, and fibromyalgia ranged from 7.5% for IC, 8.7% for vulvodynia, and 9.4% for IBS, to 11.8% for fibromyalgia, with 27.1% screening positive for multiple conditions.53 The presence of vulvodynia was associated with the presence of each of the other comorbid pain conditions, noted the researchers.

In a second study of 1,457 women with localized, generalized, or combined vulvodynia, IBS and fibromyalgia were the most common comorbidities found in patients with vulvodynia, regardless of type of vulvar pain.54 The researchers noted that at least 2 comorbid pain conditions were present in 50% of the women with vulvodynia.

A study of patients with chronic pelvic, vulvar pain (PVD) found significantly higher gray matter densities in pain modulatory and stress-related areas compared with controls.55 In several of these regions, “gray matter changes correlated with lowered pain thresholds and increased pain catastrophizing scores,” noted the researchers. In addition, an imaging study performed during painful stimulation (thumb pressure) found that, compared to controls, vulvodynia patients displayed greater levels of activation in the insula, dorsal mid-cingulate, posterior cingulate, and thalamus.56

Temporomandibular Joint Disorder

There has been significant controversy whether TMJD has a localized structural basis or should be included as
1 of the functional, chronic pain disorders. During the past decade, many investigators have concluded that TMJD fits best as a central sensitization syndrome. Epidemiologic studies have revealed a significant overlap of TMJD with fibromyalgia, as well as chronic headaches, IBS, and CFS.3,6,32 TMJD patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the central sensitization conditions, including CFS, fibromyalgia, IBS, multiple chemical sensitivities, and headache.3 Lifetime rates of IBS were particularly striking in the patient groups (CFS, 92%; fibromyalgia, 77%; TMJD, 64%) compared with controls (18%).

In 1 study, TMJD subjects with widespread pain presented with reduced pressure pain thresholds in both cranial and extracranial regions compared to TMJD subjects without widespread pain, as well as with an increase in somatic symptoms (Table 3).57 The TMJD subjects reported 1.7 comorbid pain conditions compared to 0.3 reported by controls.57

A number of psychological variables have been found to predict the onset of TMJD, including perceived stress, previous life events, and negative affect.58 Moreover, TMJD incidence was related to sociodemographic characteristics, health status, clinical orofacial factors, psychological functioning, pain sensitivity, and cardiac autonomic responses.

The presence of generalized pain is an important factor in the prevalence of TMJD in the general population.57-59 The prevalence of TMJD pain complaints was 7.2% to 8.0%, and around twice as high in women as in men. TMJD pain complaints were strongly related to the presence of other pain complaints. The level of generalized somatic symptoms correlated with pressure pain thresholds in subjects with TMJD.60

TMJD also has been associated with headaches, including migraine.61 In migraine patients, TMJD was present in 71.4%, and in 38.1% of tension-type headache patients.

There was a positive association between the number of comorbidities present and TMJD pain intensity and between the number of comorbidities present and TMJD pain duration.62 Also, the presence of migraine was positively associated with TMJD pain intensity, while the presence of CFS was positively associated with TMJD pain intensity and duration.62  

Summary

There is significant overlap in the clinical features of fibromyalgia with those of IBS, IC/PBS, chronic headaches, and TMJD. Furthermore, pathophysiologic studies demonstrate that central pain hypersensitivity is prominent in each of these disorders. Clinicians should not get concerned with the exact label for these disorders but rather recognize their common nature. This will help reduce specialty referral and excess cost associated with diagnostic testing. Furthermore, this recognition should promote a more uniform treatment program based on medications that may decrease pain sensitivity and nonpharmacologic programs that focus on multidisciplinary, patient-centered pain management.

Last updated on: September 15, 2016
Continue Reading:
Behavioral Medicine: How to Incorporate Into Pain Management

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