graph LR
Droplet_based_microfluidic_protease_activity_profiling_platform_PrAMA;_MIT_Griffith_Han["Droplet-based microfluidic protease-activity profiling platform (PrAMA; MIT Griffith/Han)"]
Central_Sensitization_and_Nociplastic_Pain["Central Sensitization and Nociplastic Pain"]
Pelvic_Pain["Pelvic Pain"]
Dysregulated_Peritoneal_Metalloproteinase_Activity["Dysregulated Peritoneal Metalloproteinase Activity"]
Hypoxia_and_Angiogenesis["Hypoxia and Angiogenesis"]
Lesion_Peritoneal_Neuroangiogenesis["Lesion-Peritoneal Neuroangiogenesis"]
Chronic_Inflammation["Chronic Inflammation"]
Peripheral_Nociceptor_Sensitization["Peripheral Nociceptor Sensitization"]
Chronic_Inflammation --> Lesion_Peritoneal_Neuroangiogenesis
Chronic_Inflammation --> Peripheral_Nociceptor_Sensitization
Hypoxia_and_Angiogenesis --> Lesion_Peritoneal_Neuroangiogenesis
Lesion_Peritoneal_Neuroangiogenesis --> Peripheral_Nociceptor_Sensitization
Peripheral_Nociceptor_Sensitization --> Central_Sensitization_and_Nociplastic_Pain
Peripheral_Nociceptor_Sensitization --> Pelvic_Pain
Central_Sensitization_and_Nociplastic_Pain --> Pelvic_Pain
Droplet_based_microfluidic_protease_activity_profiling_platform_PrAMA;_MIT_Griffith_Han --> Dysregulated_Peritoneal_Metalloproteinase_Activity
style Droplet_based_microfluidic_protease_activity_profiling_platform_PrAMA;_MIT_Griffith_Han fill:#ccfbf1
style Central_Sensitization_and_Nociplastic_Pain fill:#dbeafe
style Pelvic_Pain fill:#fef3c7
style Dysregulated_Peritoneal_Metalloproteinase_Activity fill:#dbeafe
style Hypoxia_and_Angiogenesis fill:#dbeafe
style Lesion_Peritoneal_Neuroangiogenesis fill:#dbeafe
style Chronic_Inflammation fill:#dbeafe
style Peripheral_Nociceptor_Sensitization fill:#dbeafe
graph LR
Small_Fiber_Pathology["Small Fiber Pathology"]
Neuroinflammation["Neuroinflammation"]
Central_Sensitization["Central Sensitization"]
Neuroinflammation --> Central_Sensitization
Small_Fiber_Pathology --> Central_Sensitization
style Small_Fiber_Pathology fill:#dbeafe
style Neuroinflammation fill:#dbeafe
style Central_Sensitization fill:#dbeafe
name: com_Endometriosis__Fibromyalgia
creation_date: '2026-06-26T00:00:00Z'
curation_status: CANDIDATE
notes: >-
Cross-system chronic-pain comorbidity: endometriosis is a risk factor for
later-onset fibromyalgia. Surfaced as a positive both-in-dismech ICEES EHR
signal (UNC PCD cohort, chi-square=9.0, p=2.6e-3) and corroborated by a
registry cohort reporting a ~2.8-fold increased incidence of fibromyalgia
after an endometriosis diagnosis. Directionality is A_BEFORE_B (endometriosis
precedes fibromyalgia); the proposed mechanism is central sensitization driven
by chronic visceral pain.
disease_a:
slug: Endometriosis
preferred_term: endometriosis
term:
id: MONDO:0005133
label: endometriosis
disease_b:
slug: Fibromyalgia
preferred_term: fibromyalgia
term:
id: MONDO:0005546
label: fibromyalgia
directionality: A_BEFORE_B
hypotheses:
- description: >-
Hypothesis: chronic visceral nociceptive input from endometriosis provokes
central sensitization, predisposing to later development of fibromyalgia and
chronic widespread pain.
evidence:
- reference: PMID:31131959
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by pain resulting from the underlying disease that has provoked a state of central sensitization."
explanation: >-
States the central-sensitization mechanism by which an underlying painful
disease can lead to widespread pain.
- reference: PMID:31131959
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This study shows that RA, endometriosis and IBD are all risk factors for later fibromyalgia and CWP"
explanation: >-
Establishes endometriosis as a risk factor for later-onset fibromyalgia,
supporting the A_BEFORE_B directionality.
pathophysiology:
- name: Central sensitization from chronic endometriosis pain
description: >-
Sustained visceral nociceptive signaling from endometriotic lesions may
drive central sensitization, lowering pain thresholds and predisposing to
fibromyalgia and chronic widespread pain.
biological_processes:
- preferred_term: sensory perception of pain
term:
id: GO:0019233
label: sensory perception of pain
evidence:
- reference: PMID:31131959
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For endometriosis patients the IRR for fibromyalgia was 2.83 (95% CI: 1.96-4.08) and for CWP 5.02 (95% CI: 3.10-8.13)."
explanation: >-
Quantifies the increased incidence of fibromyalgia following an
endometriosis diagnosis.
association_signals:
- source: ICEES
method: EHR_COHORT_ASSOCIATION
signal_disorder_a_id: MONDO:0005133
signal_disorder_b_id: MONDO:0005546
population: >-
ICEES KG 8-20-2024, UNC Health primary-ciliary-dyskinesia (PCD) cohort
(condition-specific base population), patient-level chi-square contingency.
mapping_notes: >-
ICEES reports this pair as a positive correlation. Chi-square is not
multiple-testing corrected and is conditioned on the PCD base population,
so it corroborates rather than establishes the association. The row quoted
is the strongest PCD cohort-year (2020).
directionality: UNKNOWN
limited_precision: true
statistics:
metrics:
- metric_type: CHI_SQUARE
metric_value: 9.046602651882589
p_value: 0.0026318341895938866
notes: >-
ICEES PCD 2020 cohort co-occurrence of endometriosis and fibromyalgia
(N=4753); significant positive association.
evidence:
- reference: ICEES:MONDO_0005133__MONDO_0005546
supports: SUPPORT
evidence_source: OTHER
snippet: "PCD_UNC_patient_2020_v6_binned_deidentified | 9.046602651882589 | 1 | 0.0026318341895938866 | 4753"
explanation: >-
ICEES UNC EHR cohort shows a significant endometriosis-fibromyalgia
co-occurrence in the 2020 PCD cohort.
- source: LITERATURE
method: LITERATURE_ASSOCIATION
population: >-
Skåne (Sweden) regional registry cohort; incidence-rate ratio of fibromyalgia
after an endometriosis diagnosis versus without.
directionality: A_BEFORE_B
statistics:
metrics:
- metric_type: IRR
metric_value: 2.83
metric_ci_lower: 1.96
metric_ci_upper: 4.08
notes: Incidence-rate ratio of later fibromyalgia among endometriosis patients.
evidence:
- reference: PMID:31131959
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "For endometriosis patients the IRR for fibromyalgia was 2.83 (95% CI: 1.96-4.08) and for CWP 5.02 (95% CI: 3.10-8.13)."
explanation: >-
Registry cohort IRR for fibromyalgia following endometriosis diagnosis.