Transcript Central Sensory Systems

Conscious
Arousal, Pain,
& Analgesia
Lesson 16
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 ~

S1
Thalamus
Brain stem
Touch
Brain
Medulla
DRG
Spinal Cord
R
ARAS
Ascending Reticular Arousal System
 inputs from CSA
 General cortical arousal
 via basal forebrain
 2 pathways ~

ARAS
BF
Thalamus

Ventral stream
 via reticular formation

Dorsal stream
 via thalamus ~
RF
CSA
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
Pain = perception
 subjective response...
 to a noxious stimulus
 Sensation = nociception
 Nociceptors
 free nerve endings ~

Spinothalamic Tract
Sensory neuron
 Glutamate (fast)
 Substance P (slow)
 Projects to spinal cord
 gray matter
 2d order neuron decussates ~

S1
Thalamus
Brain stem
Pain
Brain
Periaqueductal
Gray (PAG)
DRG
R
Spinal Cord
Substance P
& Glutamate
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 ??? ~
Periaqueductal
Gray (PAG)
Opioid
GABA
-
+
+
Descending
Analgesia
Circuit
Raphe System
5-HT
DRG
R
Spinal Cord
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
5-HT
+
Opioid Neurons
Presynaptic
inhibition
Postsynaptic
inhibition
Substance
P
Analgesia in
Spinal Cord
5-HT
+
GABA Neurons
Postsynaptic
inhibition
Substance
P
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 ~
