3j - ANS - INFLAMMATION INTERACTION IN ENDOMETRIOSIS-ASSOCIATED PAIN

Question 1

Core concept

Answer 1

• Endometriosis not only hormonal disorder but chronic inflammatory condition involving immune dysfunction & autonomic nervous system (ANS) imbalance
• Pain in endometriosis results from neuroimmune dialogue: inflammatory cytokines sensitize nerves, while
  autonomic imbalance (especially heightened sympathetic tone) amplifies pain

Question 2

Pathophysiological framework:
- inflammation
- autonomic nervous system
- neuro-immune crosstalk

Answer 2

Inflammation
- Peritoneal fluid in endometriosis patients is rich in proinflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1)
- These mediators:
o Promote angiogenesis and neurogenesis in ectopic endometrial tissue
o Increase nociceptor sensitization → persistent pelvic pain

Autonomic Nervous System (ANS)
- Chronic pain and inflammation disrupt the ANS:
o ↑ Sympathetic activity: vasoconstriction, immune modulation, hyperalgesia.
o ↓ Parasympathetic (vagal) tone: less anti-inflammatory control.
- Imbalance favors proinflammatory dominance and worsens pain perception.

Neuro-Immune Crosstalk
- Nerve fibers and immune cells communicate bidirectionally.
o Inflammatory cytokines modulate neuronal excitability.
o Neurotransmitters (ex : norepinephrine) modulate immune cell activation.
- Result: vicious cycle of inflammation → nerve growth → more inflammation

Question 3

Clinical manifestations

Answer 3

Table

Question 4

Key evidence

Answer 4

• Increased nerve fiber density in endometriotic lesions correlates with pain intensity
• Lesions are often innervated by sympathetic nerves but lack sufficient parasympathetic input, hallmark of
  neuro-immune imbalance
• Targeting both inflammation & neuro-regulation offers better control of symptoms than hormone therapy
  alone

Question 5

Therapeutic implications:
- pharmaco
- non-pharmaco

Answer 5

Pharmacological
- NSAIDs: reduce prostaglandin-driven pain but not cytokine effects.
- Hormonal therapies (e.g., GnRH agonists): reduce estrogen, thus lesion growth, but not always effective for
chronic pain.
- Neuromodulators: SNRIs, tricyclics (e.g., amitriptyline) may reduce central sensitization.

Non-Pharmacological
- Vagal nerve stimulation (VNS): enhances parasympathetic tone → anti-inflammatory effect
- Biofeedback, acupuncture, mindfulness: regulate ANS tone
- Exercise and anti-inflammatory diets: modulate systemic inflammation and stress response