NEUROANATOMY OF THE PAIN -...

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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