3g - CHRONIC STRESS, HPA AXIS & HEADACHE

Question 1

Core concept

Answer 1

• Headache disorders, especially tension-type headaches & migraine, strongly influenced by chronic psychological stress
• 2 main biological systems mediate this effect:
  o Hypothalamic-Pituitary-Adrenal (HPA) Axis
  o Autonomic Nervous System (ANS

Question 2

Mechanistic overview:
- HPA axis dysregulation
- autonomic nervous system dysfunction

Answer 2

HPA Axis Dysregulation
- Chronic stress → sustained CRF (corticotropin-releasing factor) release from hypothalamus
- Stimulates ACTH from the pituitary → triggers prolonged cortisol release from adrenal glands
- Prolonged cortisol dysregulates:
o Pain modulation systems
o Inflammatory cytokines
o Brain areas related to mood and pain perception (amygdala, hippocampus)

Autonomic Nervous System Dysfunction
- Chronic stress skews ANS balance toward:
o ↑ Sympathetic activity (“fight or flight”)
o ↓ Parasympathetic activity (vagal tone reduction)
- This imbalance leads to:
o Increased vascular reactivity and nociception
o Decreased pain threshold and poor headache coping

Question 3

Biological mediators of headache in stress

Answer 3

Table

Question 4

Neuroanatomical involvement

Answer 4

Brain structures involved in stress-pain interface:
- Hypothalamus: orchestrates HPA response.
- Amygdala: processes emotional stress.
- Periaqueductal gray (PAG) & trigeminal system => descending pain inhibition, dysregulated in chronic stress

Question 5

Types of headache associated with chronic stress

Answer 5

Table

Question 6

Clinical evidence

Answer 6

• Stress = commonly reported trigger for headache onset & exacerbation
• High-stress patients exhibit:
  o Increased frequency & intensity of headaches
  o Impaired regulation of HRV (heart rate variability)
  o Altered neuroimmune markers & pain sensitivity

Question 7

Therapeutic implications:
- behavioral / non-pharmaco
- pharmaco

Answer 7

Behavioral/Non-Pharmacological
- Biofeedback and relaxation training: restore ANS balance.
- Mindfulness and CBT: reduce HPA axis hyperactivity and anxiety.
- Physical activity: improves stress resilience and vagal tone.

Pharmacological
- Beta-blockers: modulate sympathetic tone and reduce migraine frequency.
- SSRIs/SNRIs: improve mood and modulate central pain pathways.
- Anticonvulsants (eX: topiramate): used in migraine prophylaxis