Conscious Arousal Pain Analgesia Lesson 16 States of

Conscious Arousal, Pain, & Analgesia Lesson 16

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

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

S 1 Thalamus Brain stem Touch Brain Medulla DRG Spinal Cord R

ARAS Ascending Reticular Arousal System l inputs from CSA n General cortical arousal l via basal forebrain l 2 pathways ~ n

ARAS BF Thalamus n Ventral stream l via reticular formation n Dorsal stream l via thalamus ~ RF CSA

ARAS: Reticular Formation ACh - arousal l ventral reticular formation n NE - arousal l locus coeruleus n 5 HT - arousal l raphe nucleus ~ n

ARAS: Basal Forebrain ACh arousal n Adenosine inhibits *ACh l Caffeine: adenosine inhibitor n Histamine stimulates *ACh l Antihistamines drowsiness ~ n

ARAS Pharmacology: GABA Modulated l Basal forebrain l GABA decreased arousal l GABA increased arousal n Agonists l Barbiturates, ETOH, benzodiazepines n Antagonists l picrotoxin, strychnine ~~ n

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

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

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

Pain S 1 Thalamus Brain stem Brain Periaqueductal Gray (PAG) DRG R Spinal Cord Substance P & Glutamate

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

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

Periaqueductal Gray (PAG) Opioid - GABA - + + Descending Analgesia Circuit Raphe System 5 -HT DRG R Spinal Cord

Analgesia in Spinal Cord n Raphe serotonin neuron mediates l 1. 5 -HT directly inhibits l 2. activates met-enkephalin uopioid l 3. activates GABA neuron ~~

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

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

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

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

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

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