somatosensory system and pain prof. marshall devor, ph.d. dept. of cell & animal biology and...

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Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew University of Jerusalem ecture 3: The primary somatosensory neuron 08-9 08-9 בבבבבבבבבב בבבבב בבבבבבבבבב בבבבב

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Page 1: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Somatosensory Systemand Pain

Prof. Marshall Devor, Ph.D.Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life SciencesHebrew University of Jerusalem

lecture 3: The primary somatosensory neuron

פיסיולוגיה מורחב פיסיולוגיה מורחב 08-908-9

Page 2: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

primary sensory neuron

Page 3: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

from stimulus to impulse trainfrom stimulus to impulse train……varietyvariety

1. force transmission to sensory ending2. transduction3. spike encoding

Page 4: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

primary sensory neuron

Page 5: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

neural crest

neural crest

Page 6: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Primary sensory neurons are pseudounipolarPrimary sensory neurons are pseudounipolar

bipolar

pseudounipolar

growth cone

sensoryending

Page 7: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

A

C

A

Page 8: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

100 uM

CGRPCGRP peptide neurotransmitterpeptide neurotransmitter

RTRT9797 neurofilamentneurofilament

Page 9: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew
Page 10: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Theory of "target derivedTheory of "target derivedneurotrophism"neurotrophism"

Page 11: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Matsuda et al

Page 12: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

no synaptic contacts in DRG

Page 13: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew
Page 14: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

microvilli on DRG somata

• enlarged surface area• numerous neurotransmitter and other receptor types

Page 15: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew
Page 16: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

primary sensory neurons

Page 17: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

nociceptors

Page 18: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

skin nerve muscle nerve m/sec A, A Ia, Ib, II 15-100+A III 2-15C (Remak bundle) IV 0.2-2

axonepineurialblood vessel

perineurium endoneurium

Page 19: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew
Page 20: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

node ofRanvier

internode

paranode

1-2 mm

nodal gap2 um

Schwann cellsoma

Page 21: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Schwann cell (glia)

internode 1-2 mmnode of Ranvier 1-2 um

30 um

myelin formation

Page 22: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

axon, myelin, Schwann cell, oligodendroglia

myelin formationmyelin formation

Page 23: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

axon, myelin, Schwann cell

Page 24: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

myelin formation in the CNSmyelin formation in the CNS

Schwann cell vs. oligodendroglial cell

Page 25: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

node of Ranvier

Page 26: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

contactin associated protein

Page 27: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

adult: DRG neuron adult: DRG neuron phenotypephenotype depends dependson regulation of both on regulation of both expression expression andand traffic trafficof molecules ofof molecules ofexcitability (NTs)excitability (NTs)

Page 28: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

A: LTMs: SA, RA, PC, hair A: warming, cooling, down hair, mechano-nociceptorsC: mechanical nociceptors mechano-heat nociceptors CMH polymodal nociceptors silent nociceptors

variety of primary afferent neurons variety of primary afferent neurons (stimulus encoding)(stimulus encoding)

Page 29: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

“neuronal phenotype” (correlates of sensory receptor types)

response CV

m/sec

axon

diam.

myelin neurochem. periph.morph.

A LTM 15-100 3-15m heavy glutamate central morph.

A nociceptionthermal+LTM

2-15

1st pain

1-3 m light glutamate+

peptides

transductionchannels

C most

nocicept.

0.2-2

2nd pain

<1 m none glutamate+peptides (NGF)IB4 (GDNF)

electrogenicchannels

spike shape

TTX-STTX-R

neuro-filam.

channeldistrib.

somadiameter

surface receptors

DRG peptidesDRG peptides: SP, CGRP, NPY, NT, VIP, SOM, GAL, CCK… substance P, calcitonin gene related peptide….

Page 30: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

“neuronal phenotype” (correlates of sensory receptor types)

response CV

m/sec

axon

diam.

myelin neurochem. periph.morph.

A LTM 15-100 3-15m heavy glutamate central morph.

A nociceptionthermal+LTM

2-15

1st pain

1-3 m light glut+

peptides

transductionchannels

C most

nocicept.

0.2-2

2nd pain

<1 m none glut+peptides (NGF)IB4 (GDNF)

electrogenicchannels

spike shape

TTX-STTX-R

neuro-filam.

channeldistrib.

somadiameter

surface receptors

DRG peptides: SP, CGRP, NPY, NT, VIP, SOM, GAL, CCK…

Page 31: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

Somatosensory System and Pain

Prof. Marshall Devor, Ph.D.Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life SciencesHebrew University of Jerusalem

lecture 3: The primary sensory neuron

פיסיולוגיה מורחבפיסיולוגיה מורחב

Page 32: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

spike invasion and the safety of through-conduction in DRG neurons …. why are DRG neurons excitable ?

Page 33: Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life Sciences Hebrew

NEURONsimulation

spike invasion

Conclusion: spike invasion is a design feature ofDRG neurons… but to what end ??

somatic

through-conduction