Understanding Pain Pathways

Understanding Pain

• Pain is a sensory and emotional experience linked to potential or actual tissue damage
• Sensory-Discriminative component answers "Where does it hurt?"
• Affective-Motivational component answers "How much does it hurt?"

Acute Pain Pathway (Mnemonic: NSSB)

• Nociceptors detect pain with specialized afferent neurons
• Signals travel via the dorsal root ganglion to the spinal cord
• The somatosensory cortex perceives pain
• The brain then processes the emotional and physical response

Peripheral Tissue Activation

• Tissue injury releases substances including Bradykinins, Prostaglandins, Potassium and Histamine (BPPH)

Nerve Fibers for Pain Transmission (Mnemonic: FAST & SLOW)

• Aδ fibers transmit fast, sharp pain, and are myelinated
• C fibers transmit slow, dull pain, and are unmyelinated

Gate Control Theory of Pain

• Aβ fibers (Mechanoreceptors) reduce pain signals
• They achieve this by activating an inhibitory interneuron in the dorsal horn

Ascending Pain Pathways

• Sensory-Discriminative pathway goes from the Lateral thalamus to the Somatosensory cortex, answering "Where does it hurt?"
• Affective-Motivational pathway goes from the Medial thalamus to the Anterior cingulate, Insula, and Amygdala, answering "How much does it hurt?"

Descending Pain Modulation and Opioids

• Key structures involved are PAG → RVM → Dorsal Horn
• Endogenous Opioids include β-Endorphins, Enkephalins, and Dynorphins
• The μ (Mu) Opioid Receptor is most important, targeted by morphine

Chronic and Neuropathic Pain

• Chronic pain can lead to gray matter loss in the DLPFC, ACC, and insula
• Neuropathic pain arises from nerve injury and is less responsive to opioids

Treatment Approaches

• Capsaicin activates the TRPV1 receptor to reduce chronic pain
• TMS activates the prefrontal cortex to reduce pain perception
• Antidepressants (SNRIs, TCAs) enhance descending pain inhibition
• NSAIDs & Opioids block pain signals chemically

Memory Aids

• Pain Fiber Mnemonic: "Fast A, Slow C"
• Gate Control Theory Mnemonic: "Rubbing it away" - activates Aβ fibers
• Opioid Receptor Mnemonic: "Mighty μ (Mu)" - targets pain relief

Importance of Sleep

• 7-9 hours of sleep is ideal; adults need 7.5 hours on average
• Sleep deprivation can mimic drunkenness, impairing memory, attention, and reaction time
• Chronic sleep deprivation leads to psychosis, weight gain, immune suppression, and cognitive decline
• Shift work impairs cognition and reduces sleep duration with age

Sleep Stages & Cycles

• Mnemonic: "BATS Drink Blood" (EEG wave patterns)
• Beta is the wave pattern when Awake
• Alpha waves occur when Drowsy
• Theta waves occur during Stage 1 sleep
• Sleep Spindles/K Complex are during Stage 2
• Delta waves are seen during Stages 3 & 4 (Deep Sleep)
• Beta waves appear during REM sleep, resembling the awake EEG

Sleep Stages Summary

• NREM 1 is light sleep where one might not realize they're asleep
• NREM 2 shows "Spindles & K" (Sleep spindles & K-complexes appear)
• NREM 3-4 features slow-wave sleep (SWS), deep sleep, growth, and repair
• REM involves dreaming, paralysis, and memory processing

Sleep Physiology & Brain Regions

• Mnemonic: "Sleep is a VLPO-controlled SCN show"
• VLPO (Ventrolateral Preoptic Nucleus) is the "Sleep switch"
• SCN (Suprachiasmatic Nucleus) governs the Circadian clock
• Pons & Midbrain handle REM regulation
• Hypothalamus, specifically Orexin/Hypocretin loss, contributes to Narcolepsy

Sleep Disorders

• Mnemonic: "WANDering through sleep" refers to common sleep disorders
• Wakefulness problems include Insomnia and Hyperarousal
• Apnea refers to Obstructive Sleep Apnea (OSA)
• Night terrors & sleepwalking are NREM disorders
• Daytime sleepiness indicates Narcolepsy

Key Facts about Sleep

• Narcolepsy is linked to low orexin and a "floppy sleep switch"
• Sleep Apnea involves stopping breathing, posing a heart risk
• Night terrors & sleepwalking occur during NREM stage 3-4 (NOT REM)

Why Do We Sleep

• Mnemonic: "Sleep Does More Than Restore"
• Sleep facilitates Survival & repair (Restorative)
• Sleep is crucial for Dreaming & memory consolidation

Sleep Benefits

• Sleep provides Metabolic regulation (Weight & immune function)
• Sleep supports Toxin clearance (Glymphatic system)
• Sleep Regulates mood & brain plasticity

Sleep & Mental Health

• Mnemonic: "Depressed? Reset with Rest"
• Depression reduces REM latency (Faster entry into REM)
• Sleep Deprivation Therapy can act as a short-term antidepressant
• Seasonal Affective Disorder (SAD) involves more melatonin in winter

Final Takeaways on Sleep

• Sleep is an active state
• Sleep is essential for cognition, mood, repair, and immunity
• Disruptions impact health, aging, and mental disorders

Introduction to Anxiety

• Anxiety is the brain's alarm system reacting to perceived threats
• Anxiety = "False Fire Alarm" - can ring even without real danger

Key Symptoms of Anxiety

• Mnemonic: “АНА!” (Avoidance, Hypervigilance, Arousal)
• Avoidance means steering clear of feared situations or stimuli
• Hypervigilance means being constantly on high alert
• Arousal manifests as increased heart rate, sweating, and agitation

Classification of Anxiety Disorders (DSM)

• Anxiety exists on a spectrum, not as distinct disorders
• Common disorders include Generalized Anxiety Disorder (GAD), Obsessive-Compulsive Disorder (OCD), Post-Traumatic Stress Disorder (PTSD), Panic Disorder, and Social Anxiety Disorder

Anxiety Disorders Mnemonic

• "GOPPS" (like "Oops" for anxiety mistakes!) for GAD, OCD, PTSD, Panic Disorder, Social Anxiety Disorder

Common Characteristics of Anxiety Disorders

• Comorbidity with depression is common, involving similar brain circuits
• Treatments include SSRIs, benzodiazepines, and therapy

Biological Basis of Anxiety

• Key Brain Regions Involved include "Fear Circuit" (AHP-PFC)
• Amygdala detects threats, triggers alarm
• Hippocampus contextualizes fear
• Prefrontal Cortex (PFC) rationalizes fear acting as the "brakes"

Brain Regions

• Amygdala - Alarm
• Hippocampus - History (memory)
• Prefrontal Cortex - Policeman (controls fear)

Physiological Response to Stress

• Triggered by the sympathetic nervous system (Periaqueductal Grey, Parabrachial nucleus) causes Flight-or-Fight Mechanism
• The Hormonal Response includes Cortisol, a stress hormone
• Norepinephrine (NE) triggers arousal (sweating, racing heart)
• GABA is a calming neurotransmitter, deficient in anxiety

Stress Hormones

• "Cortisol makes stress prolong, norepinephrine pumps it strong (GABA fights back to keep it calm!)"

Psychological & Experimental Studies on Anxiety

• Lang’s Anxiety Spectrum: Anxiety exists on a scale, not in isolated boxes
• Ursin’s Parachute Study: Anxiety decreases with repeated exposure
• LeDoux’s "Fast and Slow Fear Pathways": Fast: Thalamus → Amygdala → Instant Reaction, Slow: Thalamus → Cortex → Rational Response

Fear Pathway

• "Fast = Thalamus to Amygdala (T-A), Slow = Cortex adds a Delay"

Treatments for Anxiety

• Medications used: SSRIs (Prozac, Zoloft), Benzodiazepines (Xanax, Valium), Beta-Blockers, and Oxytocin
• Psychotherapy options: Cognitive Behavioral Therapy (CBT), Exposure Therapy, Mindfulness & Relaxation

Anxiety Treatments

• Mnemonic: "S.B.C." (Stay Balanced & Calm)
• SSRIs (Serotonin boost), Benzodiazepines (Boost GABA), and CBT

PTSD & Trauma Research

• The significance of levels of Cortisol is debated
• PTSD twin study points to smaller hippocampus means greater PTSD risk
• MDMA Therapy is a potential breakthrough

PTSD Causes

• "T.H.E Trauma"
• Too little cortisol
• Hippocampus shrinks
• Extreme emotional memories stay

OCD & Anxiety

• OCD uses different brain circuits (Basal Ganglia & Cortico-Thalamic Loops)
• Psychosurgery with Anterior Cingulotomy helps in severe cases
• Deep Brain Stimulation (DBS) & TMS are new experimental treatments