Psychoneuroimmunology, Polyvagal Theory & Contextual Healing – Comprehensive Study Notes

Psychoneuroimmunology (PNI) / Psycho-Immuno-Neuro-Endocrine (PINE) FRAMEWORK

• Interdisciplinary field integrating psychology, neurology, immunology & endocrinology to explain health & disease.
  • Rebecca Macy’s focus: multifactorial etiology of complex chronic illness, lifestyle interventions, community approaches & health equity.
• Core clinical objective of lecture: apply PINE to pain pathophysiology & integrative pain management.
• Learning outcomes (post-reflection):
  • Explain PINE functions/processes in pain.
  • Identify neuro-immune factors & intervention points in central sensitization.
  • Describe key tenets of Polyvagal Theory (PVT) & autonomic state’s role in pain.
  • Analyze influence of implicit learning & social-cognitive processes (placebo/contextual healing) on outcomes.

CASE STUDY – DIFFUSE PAIN & FATIGUE WITHOUT DIAGNOSIS

• Patient: weeks of aching pain & fatigue, anxiety about lost promotion, normal diagnostics ➜ rises in apprehension/frustration.
• Likely PINE processes while in waiting room:
  • Psychological: anxious rumination, negative outcome expectancy.
  • Neural: amygdala tags threat ➜ sympathetic adrenal medullary (SAM) + hypothalamic–pituitary–adrenal (HPA) axes fire.
  • Immune: T/B cells, NK cells, macrophages (\uparrow); pro-inflammatory cytokines (IL\text{-}6,\ TNF\text{-}\alpha \uparrow).
  • Endocrine: \text{Epi} \uparrow,\ \text{NE} \uparrow,\ \text{Cortisol} \uparrow
  • Metabolic: energy diverted to muscles & CV output.
  • Positive feedback loops reinforce anxiety, emotional lability, reduced PFC inhibition, sickness behaviour (depressed mood, isolation) & further endocrine changes.

STRESS RESPONSE AXES

• Subjective threat detects → Amygdala → diverges:
  • HPA AXIS
  • Hypothalamus releases CRF.
  • Pituitary releases ACTH.
  • Adrenal cortex releases cortisol.
  • Cortisol’s dual role: mobilise energy yet negative feedback anti-inflammatory brake.
  • SAM AXIS
  • Brainstem sympathetic neurons release NE.
  • NE signals immune system ➜ cytokines (IL\text{-}6, TNF\text{-}\alpha) → peripheral/central inflammation.
• Combined cascade = “inflammatory cascade.”
  • Evolutionary rationale: prepare for injury/pathogen during fight/flight.
  • Chronic/uncontrollable stress ➜ cortisol receptor desensitisation → feedback fails → positive loop, inflammation spreads.

HOMEOSTASIS vs ALLOSTASIS

• Homeostasis: dynamic baseline balance (e.g., micro-adjustments walking a balance beam).
• Allostasis: energetic expenditure to restore balance after perturbation (larger windmilling after kickball hit).
• Allostatic load: cumulative demand; Allostatic overload from repeated activation → PINE dysfunction, “weathering.”
  • Documented links with social determinants & discrimination → telomere shortening.
• Autonomic mapping: Rest = parasympathetic (ventral vagal); Allostasis = sympathetic (fight/flight/fawn); Overload may tip into dorsal vagal freeze.

BRAIN→IMMUNE, IMMUNE→BRAIN & INTERPERSONAL NEUROBIOLOGY PATHWAYS

• Brain→Immune
  • Perceived stressor → HPA/SAM activation → inflammatory cytokines → pain potentiation.
  • Intervention levers: stress appraisal, coping skills, anti-inflammatory agents, lifestyle.
• Immune→Brain
  • Peripheral cytokines activate microglia → neuroinflammation.
  • Induces sickness behaviour: depression, isolation, fatigue, risk aversion.
  • Chronic illnesses (CFS, chronic pain) show sickness-behaviour magnitude ≈ volunteers injected with endotoxin.
• Interpersonal Neurobiology
  • Social reward/motivation circuitry: Dopamine (pursuit), Oxytocin (bonding).
  • Oxytocin modulates pain; low dopaminergic tone both predicts & results from chronic pain.

CLINICAL PRESENTATIONS BENEFITTING FROM PINE PERSPECTIVE

• Diffuse/migrating/transient symptoms that evade standard diagnostics.
• Multisystem dysfunction defying categorisation.
• Inconsistent / insufficient responses (e.g., refractory migraine, TR-depression).
• Chronic fatigue, idiopathic/neuropathic pain.
• Functional Neurological Disorder (historically “hysteria”).
• Contributing contextual factors to screen:
  • Interpersonal stress, social determinants, adversity history, health beliefs (risk perception, self-efficacy).
  • Use alternative entry points: psychologic ↔ neuro ↔ endocrine ↔ immune (diagram of multiple doors).

CENTRAL SENSITIZATION & CHRONIC OVERLAPPING PAIN CONDITIONS (COPC)

• COPC list (ICD-11 recognised): fibromyalgia, TMJ, IBS, ME/CFS, endometriosis, tension/migraine headaches, chronic pelvic pain, chronic low-back pain.
• Central Sensitization = process (not diagnosis):
  • Clinical signs: Hyperalgesia, Allodynia, Global sensory hyper-responsiveness.
  • Underlying nociplastic changes:
  • CNS neuronal hyperexcitability.
  • ↓ descending inhibitory pathways.
  • ↑ activity in sensory-emotion brain regions.
  • Altered HPA function & sympathetic dominance.
  • Predisposing factors (Volchek et al.): genetics, comorbid physical/psych conditions, psychosocial factors (expanded: adversity, cognitive appraisals, affective salience, implicit learning).
• Opportunities: mind-body practices, vagal toning → shift sympathetic dominance.

POLYVAGAL THEORY (PVT)

• Developed by Stephen Porges (1994); remains theoretical, under debate.
• Vagus nerve (Cranial X) = primary parasympathetic conduit; two branches:
  • Ventral vagal (front) → relaxation, connection, safety, prosocial cues, supports “rest-digest-heal.”
  • Dorsal vagal (back) → extreme braking; shutdown, dissociation, freeze.
• Relationship with sympathetic chain:
  • At baseline: Ventral vagal.
  • Manageable threat: Sympathetic (fight/flight/fawn).
  • Overwhelming threat: Dorsal vagal freeze.
• Autonomic State determines behavioural repertoire (S-O-R model).
• Neurosception: pre-conscious detection of safety/threat via facial/vocal cues (social engagement system).
• Co-regulation: borrowing another’s ventral vagal state; cannot be faked.
• Clinical application:
  • Provider’s genuine ventral vagal tone → patient perceives safety ➜ broader treatment response options.
  • Example scenario: masked clinician verbally accosted → response varied under ventral ↔ sympathetic ↔ dorsal states.

CONTEXTUAL HEALING (Placebo Effects)

• Total treatment effect = Specific (characteristic) + Non-specific (incidental/placebo) effects.
  • Characteristic feature (e.g., PT ROM exercises) → specific effect (↑ ROM).
  • Incidental feature (e.g., patient-centred care) → non-specific effect (↑ motivation).
• Placebo = aggregated non-specific effects: expectancy, conditioning, mindset, social learning, perceived safety, interpersonal neurobiology.
• Applies to all modalities (antibiotics, acupuncture, etc.).
• Aim: leverage placebogenic factors rather than dismiss as “noise.”

INTEGRATED MAP – FOUR MODIFIABLE TARGETS IN CHRONIC/COMPLEX PAIN

1. Health Beliefs
   • Formed via sociocultural context, experiences, literacy.
   • Provider role: reframe outcome expectancies, build accurate risk perception & self-efficacy.
   • Positive expectancies → parasympathetic dominance, ↓ inflammation.
2. Health Behaviours
   • Exercise, sleep, diet, mind-body practices.
   • Moderate exercise ↑ vagal tone, supports homeostasis.
   • Behaviours ↔ beliefs bidirectionally reinforce.
3. Autonomic Arousal & Self-Regulation
   • Trauma & adversity may lock sympathetic/dorsal dominance.
   • Build capacity via breathwork, meditation, graded exposure to safety.
4. Social Support / Interpersonal Neurobiology
   • Therapeutic alliance as immediate lever.
   • Oxytocin release, co-regulation, authentic presence.

• Feedback loops:
  • Behavioural change shifts autonomic tone & inflammatory status.
  • Improved autonomic regulation enables adoption of further health behaviours.

ETHICAL, PHILOSOPHICAL & PRACTICAL IMPLICATIONS

• Recognition of systemic inequities (social defeat stress) as biological insult.
• Need for compassionate framing of psychosomatic conditions; avoid dismissive “it’s all in your head.”
• Providers’ self-care = ethical imperative; their autonomic state materially affects patient outcomes.

NUMERICAL / RESEARCH REFERENCES (selected)

• Pro-inflammatory biomarkers: IL\text{-}6 \uparrow,\ TNF\text{-}\alpha \uparrow after SAM activation.
• Telomere shortening correlates with chronic discrimination (biological aging).
• Sickness behaviours in ME/CFS equal to experimentally induced endotoxin illness severity.

EXAMPLES & METAPHORS

• Thermostat analogy: cortisol as heated air in negative feedback loop.
• Balance beam: homeostasis vs larger corrective allostasis.
• Car brakes: ventral (gentle) vs dorsal (slam) vagal activation.
• Grocery store mask incident: illustrates S-O-R & autonomic state differences.
• Still-Face Procedure: neurosception demonstration in infants.

CONNECTIONS TO PRIOR CONTENT & REAL-WORLD RELEVANCE

• Aligns with Lifestyle Medicine (exercise, diet, sleep) & Mind-Body Medicine (breath, meditation).
• Reinforces biopsychosocial pain model, central sensitization concepts introduced elsewhere in curriculum.
• Real-world: informs trauma-informed care, public-health policy on discrimination, mental-health metabolic research (“Brain Energy” by Palmer).

DISCUSSION PROMPTS (as provided)

• How do health beliefs you commonly encounter augment or hinder pain outcomes?
• Identify one incidental feature of your clinical style that could be optimised for contextual healing.
• Reflect on a personal autonomic regulation practice; how might you teach/adapt it for patients in sympathetic overdrive?
• Consider a patient with high adversity history: map interventions across the four modifiable targets.

RECOMMENDED READING (lecture list)

• Porges S. “The Pocket Guide to Polyvagal Theory.”
• Palmer C. “Brain Energy.”
• Additional texts/articles referenced in end-slide (ordered by appearance in original deck).