Fibromyalgia

1. Clinical Overview

Summary

Fibromyalgia is a chronic pain syndrome characterised by widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive dysfunction ("fibro fog"). It affects 2-4% of the population, with a female predominance (7:1 ratio). [1] The condition represents a paradigm shift in understanding chronic pain — it is not a disease of peripheral tissues, but rather a disorder of central pain processing involving amplification of sensory signals within the central nervous system. [2]

Fibromyalgia is a clinical diagnosis based on the widespread pain index (WPI) and symptom severity scale (SSS), with characteristically normal laboratory investigations and imaging. [3] The absence of inflammatory markers, structural abnormalities, and objective findings on examination distinguishes it from inflammatory rheumatological conditions. However, the pain is real, distressing, and functionally limiting.

Management is multidisciplinary and centres on patient education, graded aerobic exercise, and pharmacological interventions targeting central pain mechanisms (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids). [4] Cognitive behavioural therapy (CBT) improves pain catastrophising and functional outcomes. [5] The condition is chronic but not progressive or life-threatening, and does not cause joint damage or deformity.

Key Facts

• Prevalence: 2-4% of the global population; up to 8% in some populations [1,6]
• Sex ratio: Female:Male = 7:1 [1]
• Age of onset: Peak 30-50 years; can occur at any age [1]
• Core features: Widespread pain, fatigue, sleep disturbance, cognitive dysfunction
• Diagnosis: Clinical using 2016 ACR criteria (WPI + SSS)
• Laboratory findings: Characteristically normal CRP, ESR, ANA, RF
• Comorbidities: Depression (20-80%), anxiety (60%), IBS (30-70%), migraine (45-80%) [7]
• Treatment: Exercise (first-line), amitriptyline, duloxetine, pregabalin, CBT
• Prognosis: Chronic, fluctuating course; not progressive; does not affect mortality

Clinical Pearls

"Normal Bloods + Widespread Pain = Fibromyalgia": If inflammatory markers, autoimmune serology, and imaging are normal in the context of chronic widespread pain, fibromyalgia is highly likely. Don't over-investigate.

"Central Sensitisation Is Key": Fibromyalgia is not a peripheral musculoskeletal problem. It's a disorder of central pain amplification — increased excitability of pain-processing neurons in the CNS. [2]

"Exercise Is First-Line": Graded aerobic exercise is the most evidence-based non-pharmacological intervention, with moderate effect sizes for pain reduction. [8] Start low (e.g., 5 minutes walking), progress gradually (add 1-2 minutes per week).

"Amitriptyline Helps Sleep and Pain": Low-dose amitriptyline (10-25 mg at night) modulates central pain processing via serotonergic and noradrenergic pathways and improves sleep architecture. [9]

"Address the Biopsychosocial Model": Depression, anxiety, sleep disorders, and catastrophising are common and bidirectionally related to pain severity. Treating these improves overall outcomes. [10]

"Avoid Opioids": Strong opioids are not effective for fibromyalgia and carry risks of dependence and opioid-induced hyperalgesia. [4,11]

Why This Matters Clinically

Fibromyalgia is frequently misdiagnosed, under-recognised, or dismissed, leading to diagnostic delays averaging 2-7 years. [12] Patients often feel invalidated by healthcare providers. Providing a clear diagnosis, validating the patient's symptoms, and explaining the neurobiological basis empowers patients and improves engagement with treatment. Evidence-based management significantly improves quality of life, even though complete symptom resolution is uncommon. [13]

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2. Epidemiology

Incidence & Prevalence

Geographic and Demographic Variation

Fibromyalgia is reported worldwide across all ethnic groups. Prevalence is higher in:

• Middle-aged adults (35-60 years)
• Women (particularly perimenopausal and postmenopausal)
• Lower socioeconomic groups (possibly reflecting access to care and psychosocial stressors) [1]

Risk Factors

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3. Aetiology & Pathophysiology

Central Sensitisation: The Core Mechanism

Fibromyalgia is characterised by central sensitisation — a state of hyperexcitability of central nervous system pain-processing pathways leading to amplified perception of pain in response to normal or mildly noxious stimuli. [2]

Key Pathophysiological Features

Neurobiological Underpinnings

Genetics: Twin studies suggest heritability of ~50%. Polymorphisms in genes encoding serotonin, dopamine, and catecholamine pathways (e.g., COMT, 5-HTT, ADRB2) are implicated. [14]

Neuroendocrine dysfunction: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation with blunted cortisol responses to stress. [23]

Sleep architecture: Alpha-wave intrusion into delta-wave sleep (non-restorative sleep) may perpetuate pain amplification. [19]

Autonomic dysfunction: Sympathetic hyperactivity and parasympathetic withdrawal contribute to symptoms (tachycardia, orthostatic intolerance). [24]

This Is NOT an Inflammatory or Structural Condition

• No synovitis, joint swelling, or erosions
• No muscle inflammation (normal muscle biopsy, EMG, creatine kinase)
• Normal CRP, ESR
• Autoantibodies (ANA, RF, anti-CCP) negative
• Normal radiographs and MRI

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4. Clinical Presentation

Core Symptoms

Associated Symptoms

Signs on Examination

Historical "Tender Points": The 1990 ACR criteria required 11/18 tender points. This is no longer diagnostic (tender points are not specific and overlap with other conditions). The 2010/2016 criteria removed tender points. [3]

Red Flags: When to Reconsider Diagnosis

[!CAUTION] Consider alternative diagnosis if:

• Objective joint swelling or synovitis (inflammatory arthritis)
• Morning stiffness > 1 hour (inflammatory arthritis)
• Unintentional weight loss (malignancy, systemic disease)
• Focal neurological signs (neuropathy, myelopathy, stroke)
• Elevated inflammatory markers (CRP, ESR)
• New onset in elderly (> 65 years) (consider polymyalgia rheumatica, malignancy, paraneoplastic syndrome)
• Muscle weakness (not fatigue) (myopathy, myositis)
• Fever, night sweats (infection, malignancy, vasculitis)

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5. Differential Diagnosis

Always consider:

1. Inflammatory Rheumatological Conditions

2. Endocrine and Metabolic

3. Neurological

4. Psychiatric

5. Other

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6. Diagnostic Criteria and Investigations

2016 American College of Rheumatology (ACR) Diagnostic Criteria [3]

Fibromyalgia is diagnosed if all of the following are met:

1. Widespread Pain Index (WPI) ≥7 AND Symptom Severity Scale (SSS) ≥5 OR WPI 4-6 AND SSS ≥9

2. Generalised pain (defined as pain in at least 4 of 5 regions)

3. Symptoms present for ≥3 months

4. No other disorder that would otherwise explain the pain

Widespread Pain Index (WPI)

Number of areas (out of 19) in which patient has experienced pain in the past week:

• Shoulder girdle (left, right)
• Upper arm (left, right)
• Lower arm (left, right)
• Hip (left, right)
• Upper leg (left, right)
• Lower leg (left, right)
• Jaw (left, right)
• Chest
• Abdomen
• Upper back
• Lower back
• Neck

Score range: 0-19

Symptom Severity Scale (SSS)

Score each of the following 0-3 (0=none, 1=mild, 2=moderate, 3=severe):

1. Fatigue
2. Waking unrefreshed
3. Cognitive symptoms

Plus the extent of somatic symptoms in general (0-3):

• 0 = no symptoms
• 1 = few symptoms
• 2 = moderate number
• 3 = great deal of symptoms

Score range: 0-12

Purpose of Investigations

Investigations are to exclude other diagnoses, not to confirm fibromyalgia.

First-Line Investigations

Second-Line Investigations (if atypical features)

Imaging

• Not routinely required for fibromyalgia
• Consider: Plain radiographs of painful joints if atypical features, trauma, or focal symptoms
• MRI: Only if neurological signs (to exclude structural CNS/spinal pathology)

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7. Classification and Severity Assessment

Fibromyalgia Severity

Based on WPI and SSS scores:

Fibromyalgia Impact Questionnaire (FIQ)

A validated patient-reported outcome measure assessing:

• Physical function (10 items)
• Days feeling good / days unable to work
• Severity of pain, fatigue, sleep, stiffness, anxiety, depression

Score: 0-100 (higher = worse)

• less than 39: Mild impact
• 39-59: Moderate impact
• ≥59: Severe impact

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8. Management

Management of fibromyalgia is multidisciplinary and focuses on:

1. Patient education and validation
2. Non-pharmacological interventions (exercise, CBT)
3. Pharmacological interventions targeting central pain mechanisms
4. Treatment of comorbidities

Management Algorithm

             FIBROMYALGIA MANAGEMENT
                       ↓
┌──────────────────────────────────────────────────────────┐
│              EDUCATION & REASSURANCE                     │
├──────────────────────────────────────────────────────────┤
│  ➤ Validate the patient's pain — it is real            │
│  ➤ Explain central sensitisation (not "in your head")  │
│  ➤ Condition is chronic but not progressive/dangerous  │
│  ➤ Set realistic expectations — improvement, not cure  │
│  ➤ Avoid over-investigation and polypharmacy           │
└──────────────────────────────────────────────────────────┘
                       ↓
┌──────────────────────────────────────────────────────────┐
│          NON-PHARMACOLOGICAL (FIRST-LINE)                │
├──────────────────────────────────────────────────────────┤
│  ➤ GRADED AEROBIC EXERCISE [8]                          │
│    • Walking, swimming, cycling, aquatic exercise       │
│    • Start low (5-10 min, 2-3x/week)                   │
│    • Increase gradually (add 1-2 min/week)             │
│    • Target: 30 min, 5x/week                           │
│    • NNT = 5 for pain reduction                        │
│                                                          │
│  ➤ COGNITIVE BEHAVIOURAL THERAPY (CBT) [5]              │
│    • Reduces pain catastrophising                       │
│    • Improves coping strategies                         │
│    • Small-to-moderate effect on pain and function     │
│                                                          │
│  ➤ SLEEP HYGIENE                                         │
│    • Regular sleep schedule                             │
│    • Avoid caffeine, alcohol, screens before bed       │
│                                                          │
│  ➤ STRESS MANAGEMENT, RELAXATION, MINDFULNESS           │
│                                                          │
│  ➤ HYDROTHERAPY, HEAT/COLD THERAPY                       │
└──────────────────────────────────────────────────────────┘
                       ↓
┌──────────────────────────────────────────────────────────┐
│              PHARMACOLOGICAL OPTIONS                     │
├──────────────────────────────────────────────────────────┤
│  FIRST-LINE: [4,9]                                       │
│                                                          │
│  ➤ AMITRIPTYLINE 10-25 mg at night                     │
│    • Tricyclic antidepressant                           │
│    • Modulates serotonin/norepinephrine; improves sleep│
│    • NNT = 4 for 50% pain reduction                    │
│    • Start 10 mg; increase by 10 mg every 1-2 weeks    │
│    • Max dose: 75 mg (higher doses no added benefit)   │
│    • Side effects: Dry mouth, drowsiness, weight gain  │
│                                                          │
│  ➤ DULOXETINE 30-60 mg once daily                      │
│    • SNRI (serotonin-norepinephrine reuptake inhibitor)│
│    • NNT = 6 for 50% pain reduction                    │
│    • Good if coexisting depression                      │
│    • Start 30 mg; increase to 60 mg after 1 week       │
│    • Side effects: Nausea, dizziness, insomnia         │
│                                                          │
│  ➤ PREGABALIN 75-150 mg twice daily                    │
│    • Gabapentinoid; modulates calcium channels          │
│    • NNT = 8 for 50% pain reduction                    │
│    • Also helps anxiety                                 │
│    • Start 75 mg BD; titrate to 150 mg BD              │
│    • Max dose: 300 mg BD                                │
│    • Side effects: Dizziness, somnolence, weight gain  │
│                                                          │
│  SECOND-LINE:                                            │
│  ➤ Gabapentin 300-600 mg TDS (if pregabalin ineffective)│
│  ➤ Milnacipran (SNRI; not available in UK)             │
│  ➤ Tramadol 50-100 mg TDS (short-term; avoid long-term)│
│                                                          │
│  AVOID:                                                  │
│  ➤ Strong opioids (morphine, oxycodone, fentanyl)      │
│    • Not effective for fibromyalgia [11]                │
│    • Risk of dependence, tolerance, hyperalgesia       │
│                                                          │
│  ➤ NSAIDs — not effective (no peripheral inflammation) │
│                                                          │
│  ➤ Corticosteroids — no role                            │
└──────────────────────────────────────────────────────────┘
                       ↓
┌──────────────────────────────────────────────────────────┐
│              TREAT COMORBIDITIES                         │
├──────────────────────────────────────────────────────────┤
│  ➤ DEPRESSION: SSRIs (sertraline, fluoxetine), SNRIs   │
│  ➤ ANXIETY: CBT, SSRIs, pregabalin                     │
│  ➤ SLEEP DISORDER: Sleep hygiene, low-dose amitriptyline│
│  ➤ IBS: Dietary modification (low FODMAP), antispasmodics│
│  ➤ MIGRAINE: Preventive agents (amitriptyline, topiramate)│
└──────────────────────────────────────────────────────────┘
                       ↓
┌──────────────────────────────────────────────────────────┐
│        FOLLOW-UP & MULTIDISCIPLINARY CARE                │
├──────────────────────────────────────────────────────────┤
│  ➤ Review response at 4-8 weeks                         │
│  ➤ Titrate medications to minimum effective dose        │
│  ➤ If no response, consider alternative agent           │
│  ➤ Refer to pain clinic or rheumatology if refractory  │
│  ➤ Consider physiotherapy, occupational therapy         │
└──────────────────────────────────────────────────────────┘

Evidence Summary: Non-Pharmacological Interventions

Evidence Summary: Pharmacological Interventions

Special Populations

Pregnancy

• Non-pharmacological interventions: Exercise, CBT, physiotherapy (safe)
• Pharmacological: Avoid amitriptyline, duloxetine, pregabalin (no safety data)
• Paracetamol: Safe but limited efficacy
• Refer: To pain specialist and obstetrician for multidisciplinary management

Elderly

• Start medications at lower doses
• Increased risk of falls with amitriptyline, pregabalin (sedation, dizziness)
• Consider drug interactions and renal impairment

Renal/Hepatic Impairment

• Pregabalin/Gabapentin: Reduce dose in renal impairment (renally excreted)
• Duloxetine: Avoid in severe hepatic impairment
• Amitriptyline: Metabolised hepatically; use with caution in liver disease

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9. Complications and Comorbidities

Complications

Comorbidities

Fibromyalgia frequently coexists with other chronic pain and functional somatic syndromes:

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10. Prognosis & Outcomes

Natural History

Prognostic Factors

Better prognosis:

• Exercise adherence [8]
• Lower baseline symptom severity
• Absence of depression/anxiety
• Active coping strategies
• Engagement with CBT [5]

Worse prognosis:

• Severe baseline symptoms
• Comorbid depression, catastrophising [10]
• Opioid use [11]
• Unemployment, litigation, compensation claims

Functional Outcomes

With appropriate management:

• 30-50% report moderate improvement in pain and function [13]
• 10-15% achieve substantial improvement
• 30-40% remain symptomatic despite treatment
• Quality of life improves even if pain persists

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11. Prevention & Screening

Primary Prevention

No established primary prevention strategies (multifactorial aetiology).

General health measures:

• Regular physical activity
• Stress management
• Adequate sleep hygiene

Secondary Prevention (Early Intervention)

• Early diagnosis reduces diagnostic delay and patient distress [12]
• Early initiation of exercise and CBT may improve outcomes

Screening

• No formal screening programmes
• High index of suspicion in patients with chronic widespread pain and normal investigations

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12. Key Guidelines

EULAR (European Alliance of Associations for Rheumatology) 2017 [4]

Key Recommendations:

1. Optimal management requires non-pharmacological and pharmacological treatments
2. Exercise (aerobic and strength training) is strongly recommended
3. Psychological therapies (CBT) are recommended
4. Pharmacological options (if non-pharmacological insufficient):
   • Duloxetine (strong recommendation)
   • Pregabalin (weak recommendation)
   • Tramadol (weak recommendation, short-term only)
5. Strong opioids not recommended
6. NSAIDs not recommended
7. Individualised treatment based on pain severity, function, comorbidities

Canadian Pain Society 2012

• Multimodal therapy combining education, exercise, CBT, and pharmacotherapy
• Amitriptyline, duloxetine, pregabalin as first-line pharmacological agents

NICE (National Institute for Health and Care Excellence)

No specific NICE guideline for fibromyalgia. Chronic pain guideline (NG193, 2021) recommends:

• Exercise programmes
• Psychological therapies (ACT, CBT)
• Antidepressants for pain (amitriptyline, duloxetine)
• Avoid long-term opioids

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13. Examination Focus

High-Yield Exam Topics

Sample Viva Questions

Q1: A 42-year-old woman presents with 6 months of widespread pain, fatigue, and poor sleep. Investigations are normal. How would you approach this?

Model Answer:

"I would consider fibromyalgia as a likely diagnosis. Fibromyalgia is a chronic pain syndrome affecting 2-4% of the population, predominantly women, characterised by central sensitisation leading to amplified pain processing.

Diagnosis: I would use the 2016 ACR criteria — Widespread Pain Index (assessing 19 body regions) and Symptom Severity Scale (fatigue, unrefreshing sleep, cognitive symptoms). A score of WPI ≥7 and SSS ≥5, with symptoms > 3 months and no alternative explanation, confirms fibromyalgia.

Investigations are to exclude differentials:

• FBC, CRP, ESR (normal in fibromyalgia; elevated suggests inflammatory arthritis)
• TFTs (exclude hypothyroidism)
• Vitamin D, calcium (exclude deficiency)
• RF, anti-CCP, ANA (negative in fibromyalgia)

Management is multidisciplinary:

1. Education: Validate symptoms; explain central sensitisation; set realistic expectations
2. Non-pharmacological (first-line):
   • Graded aerobic exercise (NNT=5) — start low, progress gradually
   • CBT (improves catastrophising and coping)
3. Pharmacological:
   • Amitriptyline 10-25 mg at night (NNT=4; helps pain and sleep)
   • OR Duloxetine 60 mg (NNT=6; good if depression coexists)
   • OR Pregabalin 75-150 mg BD (NNT=8)
4. Treat comorbidities: Depression, anxiety, sleep disorder
5. Avoid: Strong opioids (ineffective), NSAIDs (no inflammation)

Follow-up at 4-8 weeks; refer to pain clinic if refractory."

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Q2: What is the pathophysiology of fibromyalgia?

Model Answer:

"Fibromyalgia is a disorder of central pain processing, specifically central sensitisation. This involves:

1. Amplified pain perception: Hyperexcitability of central pain-processing pathways (dorsal horn neurons, thalamus, cortex). Quantitative sensory testing shows reduced pain thresholds to mechanical, thermal, and pressure stimuli.

2. Impaired descending inhibition: Dysfunction of brainstem-mediated pain suppression (periaqueductal grey, rostroventral medulla). Normally, descending pathways inhibit nociception; this is impaired in fibromyalgia.

3. Neurotransmitter dysregulation:

   • Increased: Substance P (3-fold), glutamate, nerve growth factor
   • Decreased: Serotonin, norepinephrine, endogenous opioids

4. Neuroimaging evidence: Functional MRI shows increased activation of pain-processing regions (insula, anterior cingulate cortex) in response to pressure.

5. Genetic susceptibility: Polymorphisms in serotonin transporter (5-HTT), COMT, and adrenergic receptor genes.

6. Neuroendocrine dysfunction: HPA axis dysregulation with blunted cortisol responses.

7. Sleep architecture: Alpha-wave intrusion into delta-wave sleep (non-restorative sleep).

This is not a peripheral musculoskeletal condition — there is no inflammation, muscle pathology, or structural damage. The pain is generated centrally."

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Q3: Why are opioids not recommended in fibromyalgia?

Model Answer:

"Strong opioids are not recommended in fibromyalgia for several reasons:

1. Lack of efficacy: Systematic reviews and RCTs show opioids are not effective for fibromyalgia pain. NNT for 50% pain reduction is not significantly different from placebo.

2. Mechanism mismatch: Opioids target peripheral nociception and mu-opioid receptors. Fibromyalgia involves central sensitisation with impaired descending inhibition and neurotransmitter dysregulation (serotonin, norepinephrine) — opioids do not address this.

3. Endogenous opioid dysfunction: Fibromyalgia patients have reduced endogenous opioid activity, and exogenous opioids may paradoxically worsen pain processing.

4. Opioid-induced hyperalgesia: Chronic opioid use can increase pain sensitivity.

5. Dependence and tolerance: High risk of addiction, tolerance, and withdrawal.

6. Side effects: Constipation, sedation, cognitive impairment, falls.

7. Guidelines: EULAR, Canadian Pain Society, and NICE all recommend against long-term opioid use in fibromyalgia.

Alternative: Use centrally-acting agents (amitriptyline, duloxetine, pregabalin) that modulate serotonin, norepinephrine, and calcium channels."

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Common Mistakes (That Fail Candidates)

❌ Mistake 1: Saying fibromyalgia is a "diagnosis of exclusion" without recognising it has positive diagnostic criteria (2016 ACR WPI + SSS).

❌ Mistake 2: Over-investigating (e.g., ordering extensive autoimmune panels, imaging) instead of using clinical criteria.

❌ Mistake 3: Recommending NSAIDs or corticosteroids (not effective; no inflammation).

❌ Mistake 4: Recommending strong opioids (not effective; risk of harm).

❌ Mistake 5: Failing to mention exercise as first-line treatment (most evidence-based intervention).

❌ Mistake 6: Not addressing comorbidities (depression, anxiety, sleep) which significantly impact outcomes.

❌ Mistake 7: Dismissing fibromyalgia as "psychosomatic" or "not real" (invalidates patient; harms therapeutic relationship).

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14. Patient/Layperson Explanation

What is fibromyalgia?

Fibromyalgia is a long-term condition that causes widespread pain throughout the body. It's often accompanied by extreme tiredness, sleep problems, and difficulty concentrating (sometimes called "brain fog").

What causes it?

We don't know the exact cause, but it's thought to involve changes in how your brain and nerves process pain signals. Your nervous system becomes overly sensitive, making normal sensations feel painful. It's like the "volume control" for pain is turned up too high.

What are the symptoms?

• Pain all over your body (not just in one area)
• Feeling exhausted all the time, even after sleeping
• Waking up feeling unrefreshed
• Trouble thinking clearly or remembering things
• Headaches, stomach problems, sensitivity to light and noise

How is it diagnosed?

Your doctor will diagnose fibromyalgia based on your symptoms and by checking that blood tests and other investigations are normal. There's no single test for fibromyalgia.

How is it treated?

Treatment focuses on managing symptoms and improving quality of life:

1. Exercise: Regular gentle exercise (like walking or swimming) is the most helpful treatment. Start slowly and build up gradually.

2. Medications: Tablets like amitriptyline, duloxetine, or pregabalin can help reduce pain and improve sleep.

3. Talking therapies: Cognitive behavioural therapy (CBT) can help you manage pain and develop coping strategies.

4. Lifestyle: Good sleep habits, stress management, pacing activities.

Is it serious?

Fibromyalgia is not dangerous and does not damage your joints or muscles. It doesn't shorten your life. However, it can affect your daily life and ability to work. With the right treatment and self-management, many people improve.

What should I avoid?

• Strong painkillers (opioids like morphine) — these don't work for fibromyalgia and can be harmful.
• Over-exertion — pace your activities and rest when needed.
• Expecting a "cure" — fibromyalgia is a chronic condition, but symptoms can be managed.

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15. References

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2. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2-S15. doi:10.1016/j.pain.2010.09.030

3. Wolfe F, Clauw DJ, Fitzcharles MA, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46(3):319-329. doi:10.1016/j.semarthrit.2016.08.012

4. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328. doi:10.1136/annrheumdis-2016-209724

5. Bernardy K, Klose P, Welsch P, Häuser W. Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome — A systematic review and meta-analysis of randomized controlled trials. Eur J Pain. 2018;22(2):242-260. doi:10.1002/ejp.1121

6. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17(8):356. doi:10.1007/s11916-013-0356-5

7. Clauw DJ, Arnold LM, McCarberg BH. The science of fibromyalgia. Mayo Clin Proc. 2011;86(9):907-911. doi:10.4065/mcp.2011.0206

8. Bidonde J, Busch AJ, Schachter CL, et al. Aerobic exercise training for adults with fibromyalgia. Cochrane Database Syst Rev. 2017;6(6):CD012700. doi:10.1002/14651858.CD012700

9. Moore RA, Derry S, Aldington D, et al. Amitriptyline for fibromyalgia in adults. Cochrane Database Syst Rev. 2015;2015(7):CD011824. doi:10.1002/14651858.CD011824

10. Fietta P, Fietta P, Manganelli P. Fibromyalgia and psychiatric disorders. Acta Biomed. 2007;78(2):88-95. PMID: 17933276

11. Painter JT, Crofford LJ. Chronic opioid use in fibromyalgia syndrome: a clinical review. J Clin Rheumatol. 2013;19(2):72-77. doi:10.1097/RHU.0b013e3182863447

12. Choy E, Perrot S, Leon T, et al. A patient survey of the impact of fibromyalgia and the journey to diagnosis. BMC Health Serv Res. 2010;10:102. doi:10.1186/1472-6963-10-102

13. Arnold LM, Clauw DJ, McCarberg BH; FibroCollaborative. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc. 2011;86(5):457-464. doi:10.4065/mcp.2010.0738

14. Arnold LM, Fan J, Russell IJ, et al. The fibromyalgia family study: a genome-wide linkage scan study. Arthritis Rheum. 2013;65(4):1122-1128. doi:10.1002/art.37842

15. Buskila D, Neumann L, Vaisberg G, et al. Increased rates of fibromyalgia following cervical spine injury: a controlled study of 161 cases of traumatic injury. Arthritis Rheum. 1997;40(3):446-452. doi:10.1002/art.1780400310

16. Häuser W, Kosseva M, Üceyler N, et al. Emotional, physical, and sexual abuse in fibromyalgia syndrome: a systematic review with meta-analysis. Arthritis Care Res (Hoboken). 2011;63(6):808-820. doi:10.1002/acr.20328

17. Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev. 2008;8(1):41-43. doi:10.1016/j.autrev.2008.07.023

18. Okifuji A, Donaldson GW, Barck L, Fine PG. Relationship between fibromyalgia and obesity in pain, function, mood, and sleep. J Pain. 2010;11(12):1329-1337. doi:10.1016/j.jpain.2010.03.006

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Last Reviewed: 2026-01-06 | MedVellum Editorial Team