Afton L. Hassett, PsyD; Daniel J. Clauw, MD
CME/CE Released: 06/28/2010; Valid for credit through 06/28/2011
Introduction
Fibromyalgia is a disorder of the central nervous system characterized by the presence of chronic widespread pain. It affects at least 2% of the general population, primarily women.[1] Additional symptoms associated with fibromyalgia include fatigue, insomnia, nonrefreshing sleep, and cognitive "fogginess" (known as fibrofog). Patients with fibromyalgia are also likely to experience 1 or more co-occurring regional chronic pain syndromes, such as irritable bowel syndrome (IBS), interstitial cystitis, temporomandibular joint disorder, and tension headaches, over their lifetime.[2-4] For example, it has been estimated that between 32% and 70% of individuals with fibromyalgia also meet criteria for IBS.[5,6] Patients who experience multiple syndromes and/or comorbid conditions present a more complex clinical scenario that requires special consideration, and such patients tend to have worse outcomes.
This review focuses on the current knowledge regarding similarities and overlap between fibromyalgia and IBS and their treatment approaches as a basis for understanding the pathophysiology of pain.
Chronic Pain Syndromes Comorbidities
Chronic pain syndromes can co-occur with other diseases; for example, fibromyalgia has been observed in about 1 in 4 patients with rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus.[7] Wolfe[8] characterizes these patients as having varying degrees of "fibromyalgianess," characterized by varying degrees of multifocal pain, fatigue, insomnia, and memory difficulties that cannot be explained on the basis of the current understanding of the pathogenesis of their rheumatologic disorders. Similarly, IBS has been estimated to co-occur in 10%-20% of patients with inflammatory bowel disease, while 5%-33% of patients with enteric infections will subsequently go on to have chronic IBS symptoms (a condition known as postinfectious IBS).[9-11] Psychological factors such as depression and anxiety are associated with the presence of IBS-like symptoms in these patients.[12]
Psychiatric comorbidities, especially depression and anxiety, are common in chronic pain conditions, including fibromyalgia and IBS. In fibromyalgia, depression and/or anxiety are present in approximately 25% of patients,[13,14] while lifetime estimates of depression are well over 60%.[13-16] Similarly, psychiatric disorders have been identified in up to 50% of patients with functional abdominal pain.[17] The presence of psychiatric comorbidities, inadequate response to treatment, and a lack of objective evidence of disease (eg, positive lab tests and identification of a peripheral cause of pain) contributed to the belief that these pain syndromes are somatization disorders -- psychiatric in nature and a "fashionable" expression of psychological distress.[18] Terms such as "functional somatic syndromes" or "medically unexplained syndromes" have only reinforced the dualism that restricts research and treatment and can be stigmatizing for individuals affected by these illnesses.
Over the past decade, innovative research inspired by advances in the neuroscience of pain has markedly contributed to the understanding of the pathophysiology of conditions like fibromyalgia and IBS. These advances have allowed us to reliably demonstrate augmented central processing of pain and sensory information in fibromyalgia, IBS, interstitial cystitis, and temporomandibular joint disorder, resulting in new and more integrative ways of conceptualizing these conditions (characterized as "central sensitivity syndromes" or "central pain syndromes") and their treatment.[19]
Fibromyalgia and Irritable Bowel Syndrome: Understanding the Central Augmentation of Pain and Sensory Processing
There is a growing consensus among experts in the pain field that chronic pain is a disease and that the underlying mechanisms may be similar to those of fibromyalgia, regardless of whether pain is present throughout the body or localized to a specific area.[20,21] Realizing that the underlying pain was not caused by peripheral damage or inflammation, but was likely the product of central nervous system dysfunction, further increased our understanding of these disorders.
Experimental pain testing studies in fibromyalgia and IBS have also enhanced our understanding of the pathophysiology of pain and sensory processing. Although early fibromyalgia dolorimetry studies found that pain thresholds correlated with distress, expectancy, and hypervigilance,[1,22,23] recent studies using sophisticated experimental paradigms demonstrated that: (1) unlike tender-point and dolorimetry exams, the random measures of pressure pain threshold were not influenced by levels of distress of the individual; (2) patients with fibromyalgia were much more sensitive to pressure, even when these more sophisticated paradigms were used; (3) patients with fibromyalgia were not more "expectant" or "hypervigilant" than controls; and (4) pressure pain thresholds at any 4 points in the body highly correlated with the average tenderness at all 18 tender points and 4 "control points."[24,25]
In addition to heightened sensitivity to pressure, individuals with fibromyalgia and IBS also display decreased somatic thresholds to heat, cold, electrical, and sensory information other than somatic stimuli, such as auditory tones.[26-29] The notion that fibromyalgia and related syndromes like IBS might represent biological amplification of all sensory stimuli also has significant support from functional neuroimaging studies. In a seminal study using functional magnetic resonance imaging to evaluate neural processing in fibromyalgia, Gracely and colleagues[30] found that stimuli of equal pressure magnitude resulted in significant increases in the blood oxygen level-dependent signal in patients with fibromyalgia compared with control individuals. Affected areas included the primary and secondary somatosensory cortices, insula, and anterior cingulate. This finding has been replicated in fibromyalgia, and similar findings of a hyperalgesic state (including hyperreactivity of the insula) have been noted in a variety of chronic pain states, including IBS.[31] The insula plays a critical role in sensory integration; while the posterior insula is associated with sensory processing, the anterior insula is linked to the emotional processing of sensations.[32-34]
Besides the common observance of diffuse hyperalgesia/allodynia, attenuated activity of descending analgesic pathways (sometimes referred to as diffuse noxious inhibitory control [DNIC]) has been reported in several of these conditions and may contribute to pain sensitivity.[35-37] In animals and healthy humans, the repeated administration of an acutely painful stimulus typically results in a subsequent increase in pain threshold (ie, decrease of tenderness).[38] This phenomenon is known as DNIC because it involves the recruitment of descending analgesic pathways to address the painful stimulus. Diffuse noxious inhibitory control has been shown to be attenuated or absent in both fibromyalgia and IBS patients, suggesting a deficiency in descending analgesic systems.[35-37] Furthermore, in fibromyalgia and comorbid depression, the deficit in pain inhibition has been shown to be more pronounced.[39] A relative deficiency in DNIC thus appears to be one of the mechanisms of central pain augmentation and may eventually serve to help characterize subgroups of patients who might be differentially responsive to various treatment modalities.
Role of Neurotransmitters
Studies from a variety of sources support the analogy of an increased "volume control" or "gain" setting on pain and sensory processing.[20] Like essential hypertension, for which a variety of causes can result in elevated systemic blood pressure, these disorders can be characterized as "essential hypertension of pain and sensory processing pathways". As depicted in the Figure, in central pain syndromes elevated levels of neurotransmitters tend to be pro-nociceptive (left side of figure), while reduced levels of neurotransmitters that inhibit pain transmission have a tendency to increase volume control (right side of figure). To date, the endogenous opioid system is the only neurotransmitter system not found to be "out of line" in a direction that would cause augmented pain transmission. Drugs that block neurotransmitters or increase their activity typically are effective treatments for individuals with central pain syndromes.
Figure 1. Neural influences on pain and sensory processing. GABA = gamma-aminobutyric acid
CME/CE Released: 06/28/2010; Valid for credit through 06/28/2011
Introduction
Fibromyalgia is a disorder of the central nervous system characterized by the presence of chronic widespread pain. It affects at least 2% of the general population, primarily women.[1] Additional symptoms associated with fibromyalgia include fatigue, insomnia, nonrefreshing sleep, and cognitive "fogginess" (known as fibrofog). Patients with fibromyalgia are also likely to experience 1 or more co-occurring regional chronic pain syndromes, such as irritable bowel syndrome (IBS), interstitial cystitis, temporomandibular joint disorder, and tension headaches, over their lifetime.[2-4] For example, it has been estimated that between 32% and 70% of individuals with fibromyalgia also meet criteria for IBS.[5,6] Patients who experience multiple syndromes and/or comorbid conditions present a more complex clinical scenario that requires special consideration, and such patients tend to have worse outcomes.
This review focuses on the current knowledge regarding similarities and overlap between fibromyalgia and IBS and their treatment approaches as a basis for understanding the pathophysiology of pain.
Chronic Pain Syndromes Comorbidities
Chronic pain syndromes can co-occur with other diseases; for example, fibromyalgia has been observed in about 1 in 4 patients with rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus.[7] Wolfe[8] characterizes these patients as having varying degrees of "fibromyalgianess," characterized by varying degrees of multifocal pain, fatigue, insomnia, and memory difficulties that cannot be explained on the basis of the current understanding of the pathogenesis of their rheumatologic disorders. Similarly, IBS has been estimated to co-occur in 10%-20% of patients with inflammatory bowel disease, while 5%-33% of patients with enteric infections will subsequently go on to have chronic IBS symptoms (a condition known as postinfectious IBS).[9-11] Psychological factors such as depression and anxiety are associated with the presence of IBS-like symptoms in these patients.[12]
Psychiatric comorbidities, especially depression and anxiety, are common in chronic pain conditions, including fibromyalgia and IBS. In fibromyalgia, depression and/or anxiety are present in approximately 25% of patients,[13,14] while lifetime estimates of depression are well over 60%.[13-16] Similarly, psychiatric disorders have been identified in up to 50% of patients with functional abdominal pain.[17] The presence of psychiatric comorbidities, inadequate response to treatment, and a lack of objective evidence of disease (eg, positive lab tests and identification of a peripheral cause of pain) contributed to the belief that these pain syndromes are somatization disorders -- psychiatric in nature and a "fashionable" expression of psychological distress.[18] Terms such as "functional somatic syndromes" or "medically unexplained syndromes" have only reinforced the dualism that restricts research and treatment and can be stigmatizing for individuals affected by these illnesses.
Over the past decade, innovative research inspired by advances in the neuroscience of pain has markedly contributed to the understanding of the pathophysiology of conditions like fibromyalgia and IBS. These advances have allowed us to reliably demonstrate augmented central processing of pain and sensory information in fibromyalgia, IBS, interstitial cystitis, and temporomandibular joint disorder, resulting in new and more integrative ways of conceptualizing these conditions (characterized as "central sensitivity syndromes" or "central pain syndromes") and their treatment.[19]
Fibromyalgia and Irritable Bowel Syndrome: Understanding the Central Augmentation of Pain and Sensory Processing
There is a growing consensus among experts in the pain field that chronic pain is a disease and that the underlying mechanisms may be similar to those of fibromyalgia, regardless of whether pain is present throughout the body or localized to a specific area.[20,21] Realizing that the underlying pain was not caused by peripheral damage or inflammation, but was likely the product of central nervous system dysfunction, further increased our understanding of these disorders.
Experimental pain testing studies in fibromyalgia and IBS have also enhanced our understanding of the pathophysiology of pain and sensory processing. Although early fibromyalgia dolorimetry studies found that pain thresholds correlated with distress, expectancy, and hypervigilance,[1,22,23] recent studies using sophisticated experimental paradigms demonstrated that: (1) unlike tender-point and dolorimetry exams, the random measures of pressure pain threshold were not influenced by levels of distress of the individual; (2) patients with fibromyalgia were much more sensitive to pressure, even when these more sophisticated paradigms were used; (3) patients with fibromyalgia were not more "expectant" or "hypervigilant" than controls; and (4) pressure pain thresholds at any 4 points in the body highly correlated with the average tenderness at all 18 tender points and 4 "control points."[24,25]
In addition to heightened sensitivity to pressure, individuals with fibromyalgia and IBS also display decreased somatic thresholds to heat, cold, electrical, and sensory information other than somatic stimuli, such as auditory tones.[26-29] The notion that fibromyalgia and related syndromes like IBS might represent biological amplification of all sensory stimuli also has significant support from functional neuroimaging studies. In a seminal study using functional magnetic resonance imaging to evaluate neural processing in fibromyalgia, Gracely and colleagues[30] found that stimuli of equal pressure magnitude resulted in significant increases in the blood oxygen level-dependent signal in patients with fibromyalgia compared with control individuals. Affected areas included the primary and secondary somatosensory cortices, insula, and anterior cingulate. This finding has been replicated in fibromyalgia, and similar findings of a hyperalgesic state (including hyperreactivity of the insula) have been noted in a variety of chronic pain states, including IBS.[31] The insula plays a critical role in sensory integration; while the posterior insula is associated with sensory processing, the anterior insula is linked to the emotional processing of sensations.[32-34]
Besides the common observance of diffuse hyperalgesia/allodynia, attenuated activity of descending analgesic pathways (sometimes referred to as diffuse noxious inhibitory control [DNIC]) has been reported in several of these conditions and may contribute to pain sensitivity.[35-37] In animals and healthy humans, the repeated administration of an acutely painful stimulus typically results in a subsequent increase in pain threshold (ie, decrease of tenderness).[38] This phenomenon is known as DNIC because it involves the recruitment of descending analgesic pathways to address the painful stimulus. Diffuse noxious inhibitory control has been shown to be attenuated or absent in both fibromyalgia and IBS patients, suggesting a deficiency in descending analgesic systems.[35-37] Furthermore, in fibromyalgia and comorbid depression, the deficit in pain inhibition has been shown to be more pronounced.[39] A relative deficiency in DNIC thus appears to be one of the mechanisms of central pain augmentation and may eventually serve to help characterize subgroups of patients who might be differentially responsive to various treatment modalities.
Role of Neurotransmitters
Studies from a variety of sources support the analogy of an increased "volume control" or "gain" setting on pain and sensory processing.[20] Like essential hypertension, for which a variety of causes can result in elevated systemic blood pressure, these disorders can be characterized as "essential hypertension of pain and sensory processing pathways". As depicted in the Figure, in central pain syndromes elevated levels of neurotransmitters tend to be pro-nociceptive (left side of figure), while reduced levels of neurotransmitters that inhibit pain transmission have a tendency to increase volume control (right side of figure). To date, the endogenous opioid system is the only neurotransmitter system not found to be "out of line" in a direction that would cause augmented pain transmission. Drugs that block neurotransmitters or increase their activity typically are effective treatments for individuals with central pain syndromes.
Figure 1. Neural influences on pain and sensory processing. GABA = gamma-aminobutyric acid
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