Chronic pain - HKDUcme.hkdu.org/files/symposia/handouts/symposium692...2015/03/21 · Acute Pain Is distinguished as being of recent onset, transient, and usually from identifiable
30
Challenges in the Management of Challenges in the Management of Chronic pain Chronic pain 16/11/2014
♦ abnormal activation of NMDA receptors in the CNS, and long-term
potentiation
of synapses between
nociceptive
C fibers and neurons in the spinal dorsal horn
DRAFT
Multiple Types of Pain
Brain image courtesy of Apollo
MedCom.Adapted from Woolf CJ. Ann Intern Med. 2004;140(6):441-451.
Used with permission from the American College of Physicians.
Noxious peripheral
stimuli
Nerve damage
No known tissue or
nerve damage
Inflammation
Acute Nociceptive Pain
Inflammatory/Joint Pain
Neuropathic Pain
Noninflammatory/ Non-neuropathic Pain
Tissue damage
8
Presenter
Presentation Notes
PURPOSE OF THE SLIDE Present an overview of a common pain classification system. KEY POINTS Pain may be classified in different ways—by its duration, by whether it is adaptive or maladaptive in terms of avoiding noxious stimuli, or by the type of stimulus inducing it. This classification is primarily based on the type of stimulus. Acute nociceptive pain may be defined as an adaptive, transient pain in response to a noxious stimulus. Diverse stimuli provoke a nociceptive response, including temperature (eg, burns or frostbite), chemicals (eg, acidic irritation), and mechanical pressure or abrasion (eg, crushing or cutting). Acute nociceptive pain is likened to an alarm that warns of potential danger. When acute nociceptive pain occurs, pain pathway structures are normal and function normally. Inflammatory/joint pain may be defined as spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation. Pain pathway structures appear normal, but they may not function normally, especially in joint-related pain. Neuropathic pain involves spontaneous pain and hyperalgesia in association with damage to, or lesion of, the nervous system (brain or spinal cord). This is analogous to an alarm that is constantly sounding, despite the fact that there is no emergency. This pain is maladaptive. Neuropathic pain is characterized by spontaneous pain and fluctuations in pain sensitivity to stimuli. Because the structural integrity of the pain pathways has been compromised, their function is abnormal as well. Noninflammatory/non-neuropathic pain results from abnormal central processing of normal input (eg, fibromyalgia, irritable bowel syndrome, tension-type headache, noncardiac chest pain). Noninflammatory/non-neuropathic pain is a type of maladaptive pain. In this case, pain pathways appear to have normal structure, but not normal function. REFERENCE Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451.
Acute Pain♦
Is distinguished as being of recent onset, transient, and usually from identifiable cause1
♦
Acute reaction to injury or noxious stimulous2,3
♦
Short term, following an acute event (e.g., surgery)3,4
♦
Expected to end with healing3,4
Chronic Pain♦
“Can be described as ongoing or recurrent pain, lasting beyond the usual course of acute illness or injury or more than 3-6 months”1
♦
May involve changes in pain processing and perception2,3
Acute Pain Vs. Chronic PainAcute Pain Vs. Chronic Pain
1. ACPA. ACPA Consumer Guide to Pain Medication & Treatment, 2010:1-81.2. Marcus. In: Chronic Pain: A Primary Care Guide to Practical Management, 2009:37-49.3. National Pharmaceutical Council Inc. Pain: Current Understanding of Assessment, Management, and Treatments, 2001:1-101.4. ICSI. Healthcare Guideline: Assessment and Management of Chronic Pain, 2009:1-91.
Presenter
Presentation Notes
Key Points: The slide highlights key characteristics to help differentiate chronic pain as a separate condition from acute pain. Acute pain typically occurs as a consequence of injury or trauma.2 Acute pain serves an important biological function, as it warns of the potential for or extent of injury. In contrast to chronic pain, the pain resolves with healing of the underlying injury.3 Chronic pain extends beyond the period of healing, with levels of identified pathology that often are low and insufficient to explain the presence and/or extent of the pain.3 References: ACPA. ACPA Consumer Guide to Pain Medication & Treatment, 2010:1-81. Marcus DA. Physiology of Chronic Pain. Chronic Pain: A Primary Care Guide to Practical Management. New York, NY: Humana Press; 2009:37-49. National Pharmaceutical Council Inc. Pain: Current Understanding of Assessment, Management, and Treatments. Reston, VA: National Pharmaceutical Council and Joint Commission on Accreditation of Healthcare Organizations; 2001:1-101. ICSI. Healthcare Guideline: Assessment and Management of Chronic Pain, 2009:1-91.
FibromyalgiaFibromyalgia Diagnostic Criteria: Diagnostic Criteria: American College ofAmerican College of RheumatologyRheumatology (ACR)(ACR)
♦ ACR Diagnostic Criteria •
1990 Diagnostic Criteria for Fibromyalgia1
•
2010 Preliminary Diagnostic Criteria for Fibromyalgia2
−
Modified in 2011: Criteria for clinical and epidemiological studies3
1. Wolfe et al. Arthritis Rheum 1990;33:160-72.2. Wolfe et al. Arthritis Care Res (Hoboken) 2010;62(5):600-10.3. Wolfe et al. J Rheumatol 2011;38(6):1113-22.
Presenter
Presentation Notes
Cymb00042177 Abbreviations: WPI: Wide Pain Index, SS: Severity Scores Key Points: The 1990 ACR criteria were the first published for fibromyalgia. Criteria based on a systematic observation of 558 consecutive patients. The combination of widespread pain and pain in ≥11 of 18 tender point sites provided the most sensitive and specific criteria for the diagnosis of fibromyalgia.1[Pg 160, abstract] The 2010 ACR criteria for classification of fibromyalgia rely upon a case definition and diagnostic criteria (WPI ≥7 and SS ≥5) or (WPI 3-6 and SS ≥9), and not on patient’s history of pain and tender point examination.2[Pg 600, abstract, results] This clinical case definition of fibromyalgia correctly classified 88.1% of cases classified by the 1990 ACR criteria.2[Pg 600, abstract, conclusion] The 2011 modification allowed its use in epidemiological and clinical studies without the requirement for an examiner.3[Pg 1113, abstract, conclusion] Background: The 2010 ACR study included 514 previously diagnosed fibromyalgia patients (n = 258) and controls (n = 256).2[Pg 603, Results, Col 2] The 2011 modification of 2010 criteria included the elimination of the physician’s estimate of somatic symptoms and replaced it with the sum of 3 specific self-reported symptoms.3[Pg 1113, abstract, results] The modified questionnaire was administered to patients previously diagnosed with fibromyalgia (n = 729), osteoarthritis (n = 855), systemic lupus erythematosus (n = 439), and rheumatoid arthritis (n = 5210).3[/pg1114/col1/para5] Based on the 2011 modification, the following patients were diagnosed as having fibromyalgia: fibromyalgia (60%), osteoarthritis (16.8%), systemic lupus erythematosus (36.7%), and rheumatoid arthritis (21.1%).3[Pg 1113, abstract, results] References: Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33(2):160-72. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62(5):600-10. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia Criteria and Severity Scales for Clinical and Epidemiological Studies: A Modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38(6):1113-22.
1990 ACR Criteria for1990 ACR Criteria for FibromyalgiaFibromyalgia: : ClassificationClassification
♦
History of widespread pain1
•
Pain is present on the left and right sides of the body, above and below the waist, and at the axial skeleton
•
Pain is present for at least 3 months
♦
Pain in at least 11 of 18 tender point sites on digital palpation1,2
For each tender point, boxes indicate both left and right sides of the bodyPalpation should be performed with the pad of the thumb at a force of ~4 kg/cm2
The tender point is positive if the palpation is perceived as painful1. Wolfe et al. Arthritis Rheum 1990;33:160-72.2. Staud and Rodriguez. Nat Clin Pract Rheumatol 2006;2(2):90-8
Cymb00042177 Copyright Disclosure: Image: Applicable permissions and/or payment-for-use completed. [Source: Wolfe F et al. Arthritis Rheum 1990;33(2):160-72. Pg 171, Table 8] Abbreviation: ACR: American College of Rheumatology Key Points: In 1990, the ACR published its first and only fibromyalgia guideline, which defined fibromyalgia by widespread pain and palpable tender points. The ACR criteria for classification of fibromyalgia rely upon a patient’s history of pain as well as on a clinical tender point examination.1(/p171/Table8) Pain is considered widespread when it is present on the left and the right sides of the body, above and below the waist, and at the axial skeleton (cervical spine, anterior chest, thoracic spine, or low back). Pain should be present for at least 3 months.1(/p171/Table8) Pain in at least 11 of 18 tender points throughout the body. The 1990 guideline still forms the core of fibromyalgia identification. Background: The ACR study included 558 patients (293 with fibromyalgia, 265 control patients with other chronic pain conditions). Controls were age- and sex-matched with patients with fibromyalgia.1(/p162/col1/para4)(/p170/Table7) Widespread pain was found in 97.6% of patients with fibromyalgia and in 69.1% of control patients.1(p160/abstract) The combination of widespread pain and mild or greater tenderness in 11 or more of the 18 tender point sites yielded a sensitivity of 88.4% and specificity of 81.1% for the diagnosis of fibromyalgia.1(/p170/Table7)(/p168/table6) The diagnosis of fibromyalgia is valid regardless of other diagnoses. Exclusionary tests such as radiographs, antinuclear antibody titers, and thyroid hormone levels are not required for diagnosis. However, it is important to identify other rheumatic disorders that occur in association with fibromyalgia because their treatment may affect the management of fibromyalgia.1(/p171/col1/para2) References: Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33(2):160-72. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol 2006;2(2):90-8.
1990 ACR Criteria for1990 ACR Criteria for FibromyalgiaFibromyalgia:: The 18 Tender Point SitesThe 18 Tender Point Sites1,21,2
1. Wolfe et al. Arthritis Rheum 1990;33(2):160-72.2. Staud and Rodriguez. Nat Clin Pract Rheumatol 2006;2(2):90-8
•
OcciputSuboccipital
muscleinsertions
•
TrapeziusMidpoint of the upper border
•
SupraspinatusAbove the scapula spinenear the medial border
•
Greater
trochanterPosterior to thetrochanteric
prominence
•
GlutealUpper outer quadrantsof the buttocks
•
Low cervicalAnterior aspects of theintertransverse
spacesat C5-C7
•
Second ribSecond
costochondraljunctions
•
Lateral
epicondyle2 cm distal tothe
epicondyles
•
KneeMedial fat pad proximalto the joint line
Presenter
Presentation Notes
Cymb00042177 Copyright Disclosure: Image: Applicable permissions and/or payment-for-use completed. Key Points: Digital palpation on these sites is performed with an approximate force of 4 kg using the thumb pad. Whitening of the nail bed usually occurs upon exerting a pressure of ~4 kg.1(/p171/table8)2(/p91/col2/box1) For a tender point to be considered positive, the patient must state that the palpation was painful.1(/p171/Table8) At least 11 of the 18 sites must be positive for the tender point criterion to be met.1(/p171/Table8) Background: The ACR study included 558 patients (293 with fibromyalgia, 265 control patients with other chronic pain conditions). Controls were matched with fibromyalgia patients for age and sex.1(/p162/col1/para4)(/p167/table5)(/p170/Table7) The combination of widespread pain and mild or greater tenderness in 11 or more of the 18 tender point sites yielded a sensitivity of 88.4% and specificity of 81.1% for the diagnosis of fibromyalgia.1(/p168/table6) (/p170/Table7) Although the ACR criteria are the currently accepted standard for research settings, their clinical usefulness is a subject of debate. As patients with fibromyalgia tend to experience tenderness throughout the body, clinicians question the specific designation of 18 tender points. There is some question as to how often all 18 tender points are examined in clinical practice settings and if examining less than 18 tender points makes the diagnosis of fibromyalgia invalid. Practitioners also question whether the criteria need to include other associated symptoms.3(/p386/col1/para2;/col2/para1,/para2) References: Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33(2):160-72. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol 2006;2(2):90-8. Häuser W, Eich W, Herrmann M, Nutzinger DO, Schiltenwolf M, Henningsen P. Fibromyalgia syndrome: classification, diagnosis, and treatment. Dtsch Arztebl Int 2009;106(23):383-91.
Combined scoring of the Widespread Pain Index (WPI) score and the 2 Symptom Severity scores (SS1 and SS2)−
WPI Score ≥7 and SS scores ≥5 or−
WPI Score 3-6 and SS scores ≥9
•
Symptoms have been present at a similar level for ≥3 months
•
Patient does not have a disorder that otherwise explains the pain
1. Wolfe et al. Arthritis Care Res (Hoboken) 2010;62(5):600-10.2. Wolfe et al. J Rheumatol 2011;38(6):1113-22.
Presenter
Presentation Notes
Cymb00042177 Key Points: The 2010 American College of Rheumatology (ACR) criteria for classification of fibromyalgia rely upon a case definition and diagnostic criteria and not on patient’s history of pain and tender point examination. A patient satisfies modified ACR 2010 fibromyalgia diagnostic criteria if the following 3 conditions are met1:[Pg 607, Table 4] WPI ≥7 and SS Score ≥5 or WPI between 3-6 and SS Score ≥9. Symptoms have been present at a similar level for at least 3 months. The patient does not have a disorder that would otherwise sufficiently explain the pain. Background: The 2011 modification of 2010 criteria included the elimination of the physician’s estimate of somatic symptoms and replaced it with the sum of 3 specific self-reported symptoms. This clinical case definition of fibromyalgia correctly classified 88.1% of cases classified by the 1990 ACR criteria.1[Pg 600, abstract, conclusion] The modified questionnaire was administered to patients previously diagnosed with fibromyalgia (n = 729), osteoarthritis (n = 855), systemic lupus erythematosus (n = 439), and rheumatoid arthritis (n = 5210). ).2[/pg1114/col1/para5] Based on the 2011 modification, the following patients were diagnosed as having fibromyalgia: fibromyalgia (60%), osteoarthritis (16.8%), systemic lupus erythematosus (36.7%), and rheumatoid arthritis (21.1%). 2[Pg 1113, abstract, results] References Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62(5):600-10. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia Criteria and Severity Scales for Clinical and Epidemiological Studies: A Modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38(6):1113-22.
0 symptoms1 Few symptoms2 A moderate number of symptoms3 A great deal of symptoms
Presenter
Presentation Notes
Cymb00042177 [Source: Wolfe F et al. Arthritis Care Res (Hoboken) 2010;62(5):600-10. Pg 607, Table 4; Wolfe F et al. J Rheumatol 2011;38(6):1113-22. Pg 1119, Appendix] Key Points: Ascertainment1:[Pg 607, Table 4] Widespread Pain Index (WPI): Patient to note the number of areas in which he/she has had pain over the last week. Score will be between 0 and 19. Symptom Severity Score (SS-1): Fatigue, waking unrefreshed, and cognitive symptoms. For the each of these, indicate the level of severity over the past week using the following scale: 0 = No problem; 1 = Slight or mild problems; generally mild or intermittent; 2 = Moderate; considerable problems; often present and/or at a moderate level; 3 = Severe: pervasive, continuous, life-disturbing problems. The Symptom Severity Score (SS1) is the sum of the severity of the 3 symptoms. The other part of the Symptom Severity Score (SS-2) is the sum of the number of the following symptoms occurring during the previous 6 months: headaches, pain or cramps in lower abdomen, depression (0–3). The final Symptom Severity Score (SS1+SS2) score is between 0 and 12. Background: The 2011 modification of 2010 criteria included the elimination of the physician’s estimate of somatic symptoms and replaced it with the sum of 3 specific self-reported symptoms. Based on the 2011 modification, the following patients were diagnosed as having fibromyalgia: fibromyalgia (60%), osteoarthritis (16.8%), systemic lupus erythematosus (36.7%), and rheumatoid arthritis (21.1%).2[Pg 1113, abstract, results] References: Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62(5):600-10. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia Criteria and Severity Scales for Clinical and Epidemiological Studies: A Modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38(6):1113-22.
Risk Factors forRisk Factors for FibromyalgiaFibromyalgia: Environmental : Environmental FactorsFactors
♦ Environmental factors also play a role1-4
•
Physical trauma•
Early life trauma•
Emotional stress•
Acute illness•
Certain infections such as
Lyme
disease, hepatitis C, and HIV
•
Metal –
nickel allergy, mercury
1. Albin and Aloush. Arthritis Rheum 2004;50(9):3059-60 4. Neuro Endocrinol Lett. 2013;34(6):559-65.2. Smith et al. Pain Physician 2011;14(2):E217-45.3. Buskila et al. Autoimmun Rev 2008;8(1):41-3.
Presenter
Presentation Notes
Cymb00042177 Key Points: Environmental factors likely play a role in fibromyalgia.1 Environmental factors or stressors may lead to the development of fibromyalgia and include physical trauma, early life trauma, emotional stress, acute illness, and certain infections such as Lyme disease, hepatitis C, and Human Immunodeficiency Virus (HIV).2,3 References: Ablin JN, Aloush V. Causes of familial aggregation of fibromyalgia: comment on the article by Arnold et al. Arthritis Rheum 2004;50(9):3059-60; author reply 3060. Smith HS, Harris R, Clauw D. Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome. Pain Physician 2011;14(2):E217-45. Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev 2008;8(1):41-3.
Risk Factors forRisk Factors for FibromyalgiaFibromyalgia: : Familial InfluencesFamilial Influences♦
Fibromyalgia
is strongly familial (the odds ratio is 8.5 for first-
degree relatives)1
•
Genetic factors may be involved in the etiology of
fibromyalgia
and in pain sensitivity1,2
♦
Fibromyalgia
co-aggregates with major mood disorder in families1
•
Mood disorders and
fibromyalgia
may share some inherited factors
1.Arnold et al. Arthritis Rheum 2004;50(3):944-52.2.Light et al. Pain Res Treat 2012;2012:427869.
Presenter
Presentation Notes
Cymb00042177 [Source: Arnold M et al. Arthritis Rheum 2004;50(3):944-52. Pg 947, Col 2, Para 2, Pg. 949, Col 2, Para 2] Key Points: Fibromyalgia has been found to aggregate strongly in families, and co-aggregate significantly with major mood disorder. These findings have significant clinical and theoretical implications.1 Familial aggregation of fibromyalgia supports the validity of the diagnosis of fibromyalgia, which is currently diagnosed with criteria that were developed by expert consensus and limited by the lack of definitive laboratory or pathological findings. Familial aggregation of fibromyalgia suggests a possible genetic contribution to its etiology. Both tender point count and total myalgic scores were associated strongly with fibromyalgia in families, and this association was independent of the presence of fibromyalgia or major mood disorder in the families. This finding supports the validity of pressure pain thresholds in fibromyalgia and suggests that there may be inherited factors in pain sensitivity. The finding of a familial co-aggregation of fibromyalgia and major mood disorder suggests that fibromyalgia shares some familial factor or set of factors with mood disorders. Fibromyalgia may involve a combination of genetic susceptibility in addition to environmental exposure that triggers further changes in expression of the same gene(s).2 Genetic haplotypes for alpha and beta-adrenergic receptors and catechol-O-methyltransferase (COMT) confer an inherent susceptibility and are related to the risk of developing fibromyalgia and other chronic pain conditions. Background: The Arnold et al. family study of fibromyalgia1 collected medical and psychiatric diagnostic information on a total of 533 first degree relatives of 78 probands with fibromyalgia and 272 first degree relatives of 40 control probands with rheumatoid arthritis.1 The study found that fibromyalgia and reduced pressure pain thresholds aggregate in families, and fibromyalgia co-aggregates with major mood disorder in families. Thus, there are possible associations of fibromyalgia with genetic polymorphisms in monoamine-related genes.3-7 References: Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, Starck LO, Keck PE Jr. Family study of fibromyalgia. Arthritis Rheum 2004;50(3):944-52. Light KC, White AT, Tadler S, Iacob E, Light AR. Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome. Pain Res Treat 2012;2012:427869. Bondy B, Spaeth M, Offenbaecher M, Glatzeder K, Stratz T, Schwarz M, de Jonge S, Krüger M, Engel RR, Färber L, Pongratz DE, Ackenheil M. The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol Dis 1999;6(5):433-9. Gürsoy S, Erdal E, Herken H, Madenci E, Alaşehirli B. Association of T102C polymorphism of the 5-HT2A receptor gene with psychiatric status in fibromyalgia syndrome. Rheumatol Int 2001;21(2):58-61. Offenbaecher M, Bondy B, de Jonge S, Glatzeder K, Krüger M, Schoeps P, Ackenheil M. Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum 1999;42(11):2482-8. Gursoy S. Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients. Clin Rheumatol 2002;21(3):194-7. Gürsoy S, Erdal E, Herken H, Madenci E, Alaşehirli B, Erdal N. Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int 2003;23(3):104-7.
Risk Factors forRisk Factors for FibromyalgiaFibromyalgia: : Role of StressRole of Stress
♦
Fibromyalgia
patients experience stressful life events•
More stressful, negative lifetime events than healthy controls1
•
Significantly higher prevalence of all forms of childhood and adult victimization and trauma than patients with rheumatoid arthritis2
*p<.05, **p<.011. Anderberg et al. Eur Psychiatry 2000;15(5):295-301.2. Walker et al. Psychosom Med 1997;59(6):572-7.
47.552.5
65.0
23.7 21.1
0.00
20
40
60
80
100
DuringChildhood orAdolescence
During thePast Year
Prior toOnset
Females with Fibromyalgia (n = 40)Controls (n = 38)
Presenter
Presentation Notes
Cymb00042177 [Source: Anderberg UM et al. Eur Psychiatry 2000;15(5):295-301. Pg 297, Table 1a and Table 1b; Pg 298, Table 1c] Key Points: Environmental factors likely play a role in the development of fibromyalgia. Stressful and traumatic experiences are frequently reported by patients with fibromyalgia, and may contribute to the risk of fibromyalgia. Roughly half of the fibromyalgia patients experienced at least one negative life event during youth, compared with roughly one quarter of controls, while 65% experienced at least one negative event at some time prior to the onset of their condition. Conflict with husband/partner and economic problems were common types of negative events.1 Compared with rheumatoid arthritis (RA) patients, those with fibromyalgia had significantly higher lifetime prevalence rates of all forms of trauma and abuse - childhood, adult, and combinations of the two.2 Background: Anderberg et al. studied 40 female fibromyalgia patients and 38 healthy age-matched women. Patients completed a self-administered questionnaire, noting the impact of life events as very negative, negative, neutral, or positive. Controls were age-matched healthy women without widespread pain or depression and of the same socioeconomic status as patients.1 47.5% of the patients (n = 40) had experienced at least one negative life event as children or adolescents, as compared to 23.7% of the controls (n = 38): p<.05. Bullying was significantly more common in fibromyalgia patients than in healthy controls. 51% of patients experienced at least one very negative life event within the previous year prior to examination, compared to 24.5% of controls. 65% of patients experienced a negative life event prior to onset of fibromyalgia, while 55% experienced a positive life event prior to onset of fibromyalgia. Conflict with spouse or partner and economic problems were common. (No control data is available since no onset occurred in controls.) Walker et al. compared 36 patients with fibromyalgia to 33 with RA through structured interviews and self-report measures exploring patient histories of sexual, physical, and emotional trauma and abuse.2 Particular forms of maltreatment in childhood did not seem to have specific effects. In adults with fibromyalgia, however, a history of physical assault strongly correlated with unexplained pain. The severity of trauma correlated significantly with measures of physical disability and psychiatric distress, illness adjustment, personality, and quality of sleep. These findings were not borne out in patients with RA.2 References: Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L. The impact of life events in female patients with fibromyalgia and in female healthy controls. Eur Psychiatry 2000;15(5):295-301. Walker EA, Keegan D, Gardner G, Sullivan M, Bernstein D, Katon WJ. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: II. Sexual, physical, and emotional abuse and neglect. Psychosom Med 1997;59(6):572-7.
Is There a Pathological Link Between Stress andIs There a Pathological Link Between Stress and FibromyalgiaFibromyalgia??♦
Disturbances in the stress-response systems in
fibromyalgia
involve•
Hypothalamic-pituitary-adrenal (HPA) axis −
Some studies show or suggest a mild-moderate alteration in the dynamic function of the HPA axis in patients with fibromyalgia1-3
•
Autonomic nervous system dysfunction4
−
Impaired sympathetic response to stressors−
Altered heart rate variability−
Some patients with severe
fibromyalgia
may have a dorsal root ganglia sodium channelopathy5
1.Clauw
and
Chrousos.
Neuroimmunomodulation 1997;4(3):134-53.2.Mease. J Rheumatol Suppl 2005;75:6-21.3.Lyon et al. Pain Med 2011;12(8):1167-78.
4. Petzke and Clauw. Curr Rheumatol Rep 2000;2(2):116-23.5. Vargas-Alarcon et al. BMC Musculoskelet Disord 2012;13(1):23.
Presenter
Presentation Notes
Cymb00042177 Key Points: Patients with fibromyalgia may have alterations in the dynamic function of the hypothalamic-pituitary-adrenal (HPA) axis.1-3 Patients may also experience autonomic abnormalities.4 However, no consistent HPA or autonomic abnormality has been found in the majority of patients.1 Background: Studies of the HPA axis in fibromyalgia have found: Reduced adrenocorticotropic hormone (ACTH) response to controlled hypoglycemic stress.6 Delayed ACTH response to interleukin-6 (IL-6).7 Studies of the autonomic nervous system have found4,5: Reduced vasoconstrictor responses to acoustic and cold stressors. Reduced epinephrine response to hypoglycemic stress. Altered heart rate variability (reduced heart rate response to exercise and variability following tilt-table testing as well as response to orthostatic stress). Some patients with severe fibromyalgia may have a dorsal root ganglia (DRG) sodium channelopathy (DRG are sympathetic-nociceptive short-circuit sites and sodium channels located in DRG that act as molecular gatekeepers for pain detection).5 References: Clauw DJ, Chrousos GP. Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation 1997;4(3):134-53. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl 2005;75:6-21. Lyon P, Cohen M, Quintner J. An evolutionary stress-response hypothesis for chronic widespread pain (fibromyalgia syndrome). Pain Med 2011;12(8):1167-78. Petzke F, Clauw DJ. Sympathetic nervous system function in fibromyalgia. Curr Rheumatol Rep 2000;2(2):116-23. Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M. A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia. BMC Musculoskelet Disord 2012;13:23. Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL. Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 1999;106(5):534-43. Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL, Chrousos GP, Pillemer SR. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia. Arthritis Rheum 2000;43(4):872-80.
Is There a Pathological Link Between Stress andIs There a Pathological Link Between Stress and FibromyalgiaFibromyalgia? ? (Cont.)(Cont.)
♦
Stress and
proinflammatory
cytokines •
Some stressors may induce the production of
proinflammatory
cytokines1
•
Inflammatory state was accompanied by an altered stress response
in
fibromyalgia
patients; demonstrated by high circulating levels of IL-8, CRP,
cortisol, and increased systemic levels of
noradrenaline
and eHsp722
•
Proinflammatory
cytokines can induce physiologic, behavioral, and hormonal changes (sickness symptoms) that include exaggerated pain responses
(hyperalgesia)3
•
Some cytokines induce
neuroendocrine
and central
monoaminergic
changes similar to those thought to be associated with depression and pain enhancement4
3. Watkins and Maier. Annu Rev Psychol 2000;51:29-57.4. Anisman and Merali. Ann Med 2003;35(1):2-11.
Presenter
Presentation Notes
Cymb00042177 Abbreviations: IL: interleukin, CRP: C-reactive protein, Key Points: Chronic stress may induce cytokine expression in the brain; cytokines, in turn, may contribute to pain enhancement in conditions like fibromyalgia. The link between cytokines and fibromyalgia has not been firmly established. Background: Fibromyalgia patients showed an inflammatory state accompanied by an altered stress response. An increased release of pro-inflammatory cytokines by monocytes, and increased activation of the neutrophils’ functional capacity were also observed in these patients.2 Proinflammatory cytokines include interleukin-1, tumor necrosis factor, and interleukin-6. These cytokines are believed to be key mediators of the immune-to-brain communication.3 During an immune challenge, these cytokines are involved in the induction of the “sickness response,” which includes changes in behavior and physiology that enhance survival.1,3 The sickness response includes fever, increased sleep, decreased food and water intake, etc. Recent evidence has emerged that suggests that proinflammatory cytokines may be released in response to stress and that exaggerated pain responses may also be part of the classic sickness response.1,3 Cytokines are hypothesized to induce depression or pain through modulation of the hypothalamic-pituitary-adrenal (HPA) axis (glucocorticoid resistance),4 downregulation of synthesis of serotonin,4 or modulation of the release of neurotransmitters such as Substance P.5 References: Maier SF. Bi-directional immune-brain communication: Implications for understanding stress, pain, and cognition. Brain Behav Immun 2003;17(2):69-85. Watkins LR, Maier SF. The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol 2000;51:29-57. Bote ME, García JJ, Hinchado MD, Ortega E. Inflammatory/stress feedback dysregulation in women with fibromyalgia. Neuroimmunomodulation 2012;19(6):343-51. Anisman H, Merali Z. Cytokines, stress and depressive illness: brain-immune interactions. Ann Med 2003;35(1):2-11. Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: Implications for clinical pain. In: Machelska H and Stein C, eds. Immune Mechanisms of Pain and Analgesia. New York, New York: Eurekah.com and Kluwer Academic/Plenum Publishers; 2003.
Evaluation ofEvaluation of FibromyalgiaFibromyalgia: Characteristic : Characteristic Clinical FeaturesClinical Features♦
Widespread body aches, pains, and tenderness1
♦
Fatigue1
♦
Cognitive impairment2
♦
Sleep disturbance1
♦
Morning stiffness1
♦
Prior depressive and anxiety symptoms1
♦
Impaired social and occupational functioning2
1.Wolfe et al. Arthritis Rheum 1990;33(2):160-722.Mease
et al. J Rheumatol 2005;32(11):2270-7.
Presenter
Presentation Notes
Cymb00042177 Abbreviation: ACR: American College of Rheumatology Key Points: Using the ACR diagnosis criteria as a starting point, researchers identified additional domains of fibromyalgia, including pain, fatigue, patient global, sleep quality, health-related quality of life, multidimensional functioning, depression, and treatment side effects.2 Virtually all patients describe severe fatigue. This may be described as being physically and emotionally drained.3 Sleep disturbance is typically described as unrefreshing sleep. In addition, patients frequently report difficulty falling and staying asleep.3 Background: Although only widespread pain and tenderness are included in the ACR criteria,1 other symptoms commonly occur in patients with fibromyalgia, and the clinical presentation of fibromyalgia is heterogeneous. In the study that established the ACR criteria, 73% to 85% of patients with fibromyalgia reported fatigue, sleep disturbance (nonrestorative sleep or insomnia), and morning stiffness. “Pain all over”, paresthesias, headache, and anxiety were experienced by 45% to 69% of patients, and co-occurring irritable bowel syndrome, sicca symptoms, and Raynaud’s phenomenon were less common (<35%).1 Many patients with fibromyalgia also report weakness, forgetfulness, concentration difficulties, urinary frequency, dysmennorrhea history, subjective swelling, and restless legs. Recently, a group of fibromyalgia researchers ranked key domains and outcome measures to help standardize and improve the quality of outcomes research in fibromyalgia. Some domains consistently ranked as important included: pain, fatigue, impairment in social or occupational function, sleep disturbance, quality of life, cognitive problems (problems with attention, concentration or organization), depression, tenderness, and anxiety.2 References: Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33(2):160-72. Mease PJ, Clauw DJ, Arnold LM, Goldenberg DL, Witter J, Williams DA, Simon LS, Strand CV, Bramson C, Martin S, Wright TM, Littman B, Wernicke JF, Gendreau RM, Crofford LJ. Fibromyalgia syndrome. J Rheumatol 2005;32(11):2270-7. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl 2005;75:6-21.
Evaluation ofEvaluation of FibromyalgiaFibromyalgia:: ComorbidComorbid Medical DisordersMedical Disorders11
1.Yunus. Pain Res Treat 2012;2012:584573.
Disorder % Prevalence, Mean (Range)
Irritable bowel syndrome 40.7 (20.0-65.0)
Temporomandibular disorder 23.7 (13.0-52.0)
Headaches (all) 26.3 (10.0-40.0)
Tension-type headache 29.7 (23.0-36.4)
Migraine 16.0 (10.0-22.0)
Mixed (tension-type and migraine) 38.2 (36.4-40.0)
Interstitial cystitis 15.4 (12.0-22.4)
Chronic fatigue syndrome 55.2 (15.6-80.0)
Vulvar vestibular syndrome 23.4 (15.6-31.2)
GulfWar syndrome 17.6 (2.0-33.8)
Presenter
Presentation Notes
Cymb00042177 [Source: Yunus MB. Pain Res Treat 2012;2012:584573. Pg 3, Table 1] Key Points: Patients with fibromyalgia experience a variety of unexplained comorbid medical disorders.1 The presence of these comorbid conditions in patients with fibromyalgia and the familial aggregation of the disorders support the hypothesis that they may have common physiologic abnormalities.2 Background: This paper describes the prevalence of fibromyalgia among other members of central sensitivity syndromes (CSS).1 An increased prevalence of fibromyalgia was observed in other chronic pain conditions with structural pathology, for examples, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease.1 Evidence exists that several of these disorders tend to aggregate within families.2 The familial aggregation findings are based on a study of 533 relatives of 78 probands with fibromyalgia and 272 relatives of 40 probands without fibromyalgia. Probands with and without fibromyalgia, together with their first-degree relatives, were evaluated using structured diagnostic interviews.2[Abstract] References: Yunus MB. The prevalence of fibromyalgia in other chronic pain conditions. Pain Res Treat 2012;2012:584573. Hudson JI, Arnold LM, Keck PE Jr, Auchenbach MB, Pope HG Jr. Family study of fibromyalgia and affective spectrum disorder. Biol Psychiatry 2004;56(11):884-91.
Evaluation ofEvaluation of FibromyalgiaFibromyalgia:: ComorbidComorbid Psychiatric DisordersPsychiatric Disorders11
1.Arnold et al. J Clin Psychiatry 2006;67(8):1219-25.
Disorder Lifetime Prevalence Rates (%)
Major mood disorder
Major depressive disorder
Bipolar disorder
73
62
11
Any anxiety disorder
Panic disorder
Posttraumatic stress disorder
Social phobia
Obsessive compulsive disorder
56
29
21
19
7
Presenter
Presentation Notes
Cymb00042177 [Source: Arnold LM et al. J Clin Psychiatry 2006;67(8):1219-25. Pg 1221, Table 1] Abbreviations: SCID: Structured Clinical Interview for DSM-IV, DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, OCD: obsessive-compulsive disorder, PTSD: post-traumatic stress disorder Key Points: This study evaluated 108 individuals with fibromyalgia and 228 individuals without fibromyalgia. The table in the slide shows the prevalence rates of several mood and anxiety disorders found in this sample.1 There is significant psychiatric comorbidity in fibromyalgia patients.1 Background: In a separate, community based study,2 several thousand women were phone screened and those with symptoms and history consistent with fibromyalgia were brought in for further diagnostic evaluation of both fibromyalgia and psychiatric disorders (by SCID). This study found that in women who met diagnostic criteria for fibromyalgia: Current MDD rates were >3 times higher in women with fibromyalgia (this study did not find higher rates of bipolar disorder). [Abstract] Women with fibromyalgia had approximately a 5-fold increase in the risk for lifetime anxiety disorders, particularly OCD and PTSD. [Pg 122, Col 1, Para 4] References: Arnold LM, Hudson JI, Keck PE, Auchenbach MB, Javaras KN, Hess EV. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry 2006;67(8):1219-25. Raphael KG, Janal MN, Nayak S, Schwartz JE, Gallagher RM. Psychiatric comorbidities in a community sample of women with fibromyalgia. Pain 2006;124(1-2):117-25.
