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NEUROANATOMYOF THE PAIN
Miklós PalkovitsHungarian Academy of Sciences/Semmelweis University, Hungary
Types of nociceptors
1. mechanical nociceptors rapid (5-30 m/s) conduction
2. thermal nociceptors rapid (5-30 m/s) conduction
(selective to heat or cold)
3. polymodal nociceptors slow (0.5-2 m/s) conduction
(mechanical, heat, chemical)
NOCICEPTORS
Primary afferents
Aδδδδ nociceptor fibers (small-myelinated fibers) GLU + SP + CGRP
sharp, pricking pain
termination: lamina I
lamina IIa
lamina V
contralateral lamina V
C fibers (unmyelinated fibers) GLU + SP + CGRP
slow, burning pain
C mechanoreceptor fibers
termination: lamina IIb
C nociceptive fibers
termination: like Aδ fibers
glutamate
aspartate
substance P
CGRP
somatostatin
VIP
galanin
dynorphins
Colocalizations: GLU + SP
GLU + CGRP
GLU + SP + CGRP
NEUROTRANSMITTERS IN THE SPINAL GANGLIA
MAJOR CELL TYPES IN THE DORSAL HORNOF THE SPINAL CORD
fusiform cellsmultipolar cellspyramidal cellsflatted cells
islet cellsstar-shaped cells
stalked cellsvertical cellsinverted stalk cells
islet cells3rd type (enkephalin) cells
pyramidal cells“antenna”-like cells
pyramidal cells“small cell” types
projection neurons
inhibitory interneurons
excitatory interneurons
inhibitory interneurons
projection neurons
projection neurons
lamina I.(marginal zone)
lamina II.(gelatinous layer)
lamina III.
lamina IV.
lamina V.
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
terminals
thalamus (VPL) -sensory cortex
activity
localization anddiscrimination of the pain
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
spinoreticular tract
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
brainstem NE neurons,reticular formation
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
activation of thenoradrenergic system
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
spinoreticular tract
spinohypothalamic tract
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
brainstem NE neurons,reticular formation
hypothalamus
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
activation of thenoradrenergic system
pain-evoked endocrineresponses
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
spinoreticular tract
spinohypothalamic tract
spinomesencephalic tract
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
brainstem NE neurons,reticular formation
hypothalamus
periaqueductal central gray
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
activation of thenoradrenergic system
pain-evoked endocrineresponses
pain inhibition
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
spinoreticular tract
spinohypothalamic tract
spinomesencephalic tract
sympatho-adrenal reflex
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
brainstem NE neurons,reticular formation
hypothalamus
periaqueductal central gray
intermediolateral cell column- vegetative ganglia
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
activation of thenoradrenergic system
pain-evoked endocrineresponses
pain inhibition
pain-evoked autonomicresponses (“alarm” reaction)
PAIN-CONDUCTING PATHWAYS AND REFLEX ARCHES
pathways
spinothalamic tract
spinoreticulothalamic tract
spinoreticular tract
spinohypothalamic tract
spinomesencephalic tract
sympatho-adrenal reflex
defense (“flexor-extensor”)reflex
terminals
thalamus (VPL) -sensory cortex
midline thalamic nuclei -limbic cortex
brainstem NE neurons,reticular formation
hypothalamus
periaqueductal central gray
intermediolateral cell column- vegetative ganglia
spinal motoneurons
activity
localization anddiscrimination of the pain
pain motivation, affectiveand behavioral responses
activation of thenoradrenergic system
pain-evoked endocrineresponses
pain inhibition
pain-evoked autonomicresponses (“alarm” reaction)
pain-evoked defensereactions
PAIN-RELATED CORTICAL REGIONS
1) Primary sensory cortex Broadman 3,1,2
2) Secondary sensory cortex Broadman 5,7b
3) Anterior cingulate cortex Broadman 24
4) Ventrolateral orbital cortex Broadman 11
= sensory-discriminative
= spatially directed attention
= motivational affective
= motivational affective
SPINOTHALAMICTRACT
SPINORETICULOTHALAMICTRACT
phylogenetically new
pain localization anddiscrimination
monosynaptic
contralateral
ventral posterolateralthalamic nucleus
phylogenetically old
motivational behavior
polysynaptic
bilateral
midline thalamic nuclei
CORTEX
LIMBIC SYSTEM
HYPOTHALAMUS
PONTINE TEGMENTUM
MEDULLA OBLONGATA
PERIPHERY
SPINAL EFFERENTS
VAGAL EFFERENTS NTS
ENKEPHALINSOMATOSTATINSUBSTANCE PCCKNEUROTENSINNPYDYNORPHINBOMBESIN
viscerosensory
TARGET AREAS OF THE ANALGETIC EFFECT OF OPIATESAND CANNABINOIDS
β-endorphin
enkephalins
dynorphins
endomorphins
nociceptin
anandamide
location of the cells
hypothalamus
central gray
dorsal horn inhibitoryinterneurons
central gray
dorsal root ganglion
dorsal root andGasserian ganglia
spinal cordhypothalamuscentral grayventral medulla
target areas
periaqueductal central gray(enkephalin and dynorphin cells)
rostral ventromedial medulla(5-HT/SP/TRH cells)
dorsal horn projection neurons
rostral ventrolateral medulla(A5-subcoeruleus NE cells)
lamina I.-IV.(presynaptic inhibition on primary afferents)
dorsal horn (lamina I.-II.)spinal trigeminal nucleus
dorsal horn, limbic cortex
dynorphin B and enkephalin cellsβ-endorphin cellsenkephalin cellsGABA cells