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Conscious Arousal, Pain, & Analgesia

Dive into the mechanisms of consciousness and pain perception, exploring sensory pathways, arousal systems, analgesic circuits, and pharmacological interventions. Understand nociception, analgesia, and sensory processing in the brain. Discover how different neurotransmitters and drugs modulate arousal and pain responses in the body.

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Conscious Arousal, Pain, & Analgesia

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  1. Conscious Arousal, Pain, & Analgesia Lesson 16

  2. States of Consciousness/Arousal A. Classical Sensory Afferents • CSA B. Thalamus C. Ascending Reticular Arousal System • ARAS D. Cortical Feedback ~

  3. Classical Sensory Afferents • Sensory information • external - from environment • internal - somatosensory • Most direct input to brain • Rapid • *point-to-point specificity • Also to reticular formation • slower, indirect input ~

  4. S1 Thalamus Medulla Touch Brain Brain stem DRG Spinal Cord R R

  5. ARAS • Ascending Reticular Arousal System • inputs from CSA • General cortical arousal • via basal forebrain • 2 pathways ~

  6. ARAS • Ventral stream • via reticular formation Thalamus BF RF CSA • Dorsal stream • via thalamus ~

  7. ARAS: Reticular Formation • ACh -  arousal • ventral reticular formation • NE -  arousal • locus coeruleus • 5HT -  arousal • raphe nucleus ~

  8. ARAS: Basal Forebrain • ACh  arousal • Adenosine inhibits *ACh • Caffeine: adenosine inhibitor • Histamine stimulates *ACh • Antihistamines drowsiness ~

  9. ARAS Pharmacology: GABA • GABA Modulated • Basal forebrain • ­GABA decreased arousal • ¯ GABA increased arousal • Agonists • Barbiturates, ETOH, benzodiazepines • Antagonists • picrotoxin, strychnine ~~

  10. What four letter word might come to mind when you smash your hand in a car door?

  11. Pain • Pain = perception • subjective response... • to a noxious stimulus • Sensation = nociception • Nociceptors • free nerve endings ~

  12. Spinothalamic Tract • Sensory neuron • Glutamate (fast) • Substance P (slow) • Projects to spinal cord • gray matter • 2d order neuron decussates ~

  13. Pain S1 Thalamus Substance P & Glutamate Brain Brain stem Periaqueductal Gray (PAG) DRG Spinal Cord R

  14. Behavioral Analgesia • Not always adaptive to attend to injury • fighting, fleeing, mating • Decreases... • nociception • subjective experience • Temporary effects • Opioid-mediated • aka Endorphins ~

  15. Behavioral Analgesia • Naloxone sensitive: • Stress (e.g., Battlefield & Predation) • Acupuncture • Placebo Effects • NOT sensitive to naloxone • Hypnosis • Meditation ??? ~

  16. - + - DescendingAnalgesiaCircuit GABA Opioid Periaqueductal Gray (PAG) + Raphe System 5-HT DRG R Spinal Cord

  17. Analgesia in Spinal Cord • Raphe serotonin neuron mediates • 1. 5-HT directly inhibits • 2. activates met-enkephalin • opioid • 3. activates GABA neuron ~~

  18. Opioid Neurons - - Analgesia in Spinal Cord 5-HT + Presynaptic inhibition Postsynaptic inhibition - Substance P

  19. GABA Neurons - Analgesia in Spinal Cord 5-HT + Postsynaptic inhibition Substance P

  20. Nonopioid Analgesia • Naloxone bocks opioid-mediated analgesia • Induced by footshock • Tail flick test • Long intermittent (30 min) • naloxone  no analgesia • Brief continuous (3 min) • naloxone  still some analgesia • Suggests nonopioid analgesic systems ~

  21. Nonopioid Analgesia • NMDA (N-methyl-D-aspartate) • Glutamate receptor • NMDA antagonist (MK-801) + naloxone • blocks analgesia in males rats • female rats: attenuated • Estrogen/progesterone analgesia • Ovariectomized female rats • ¯ nonopioid analgesia ~

  22. Nonopioid Analgesia • Developed from frog skin toxin • epibetadine • 20x more potent than morphine • non-specific binding – too toxic for humans • Found ACh agonist with similar structure • Altered  ABT-594 ~

  23. Cholinergic-mediated analgesia • ABT-594: cholinergic agonist • Comparable to opiate analgesia • nACh-R in raphe nucleus • Fewer side effects • no euphoria • no constipation • no respiratory depression • Conotoxins from cone snail • neuropathic pain ~

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