Conscious Arousal, Pain,
& Analgesia
Lesson 17
States of Consciousness/Arousal
A. Classical Sensory Afferents CSA
B. Thalamus
C. Ascending Reticular Arousal System ARAS
D. Cortical Feedback ~
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 ~
Spinal Cord
Touch
R
DRG
Medulla
S1
R
Thalamus
Brain stem
Brain
ARAS
Ascending Reticular Arousal System inputs from CSA
General cortical arousal via basal forebrain 2 pathways ~
CSA
RF
ThalamusBF
ARAS
Ventral stream via reticular formation
Dorsal stream via thalamus ~
ARAS: Reticular Formation
ACh - arousal ventral reticular formation
NE - arousal locus coeruleus
5HT - arousal raphe nucleus ~
ARAS: Basal Forebrain
ACh arousal Adenosine inhibits *ACh
Caffeine: adenosine inhibitor Histamine stimulates *ACh
Antihistamines drowsiness ~
ARAS Pharmacology: GABA
GABA Modulated Basal forebrain GABA decreased arousal GABA increased arousal
Agonists Barbiturates, ETOH, benzodiazepines
Antagonists picrotoxin, strychnine ~~
What four letter word might come to mind when you smash your hand in a car door?
Pain = perception subjective response... to a noxious stimulus
Sensation = nociception Nociceptors free nerve endings ~
Pain
Spinothalamic Tract
Sensory neuron Glutamate (fast) Substance P (slow)
Projects to spinal cord gray matter 2d order neuron decussates ~
Pain
Thalamus
S1
DRG
RSubstance P& Glutamate
Spinal Cord
Brain stem
Brain
PeriaqueductalGray (PAG)
Behavioral Analgesia
Not always adaptive to attend to injury fighting, fleeing, mating
Decreases... nociception subjective experience
Temporary effects Opioid-mediated
aka Endorphins ~
Behavioral Analgesia
Naloxone sensitive: Stress (e.g., Battlefield & Predation) Acupuncture Placebo Effects
NOT sensitive to naloxone Hypnosis Meditation ??? ~
Spinal Cord
DRG
R
PeriaqueductalGray (PAG)
-Opioid
+
GABA
-DescendingAnalgesia
Circuit
Raphe System 5-HT
+
Analgesia in Spinal Cord
Raphe serotonin neuron mediates 1. 5-HT directly inhibits 2. activates met-enkephalin
opioid 3. activates GABA neuron ~~
Analgesia in Spinal Cord
Substance P
Postsynaptic inhibition
Presynaptic inhibition
-
Opioid Neurons
--
5-HT
+
Analgesia in Spinal Cord
Substance P
Postsynaptic inhibition
GABA Neurons
-
5-HT
+
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 ~
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 ~
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 ~
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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