Lecture 14 - 3rd Asessment - Pain Transmission System

PAIN TRANSMISSION SYSTEM • Definition and classification of pain • Pain-related information – PNS, CNS • Endogenous mechanisms of analgesia

PAIN – CLASSIFICATION • Perceptive – Nociception Descrimination • Reactive – Behavior response

PAIN – CLASSIFICATION • Nociceptive – Nociceptor • Neuropathic – Nerve damage • Symptoms – Allodymia, hyperalgesia, analgesia

Brain

Spinal Cord Receptor

First-order neuron )Dorsal root ganglion(

Third order neuron )Thalamus(

Second order neuron )Dorsal horn(

DESCENDING CONTROL PATHWAY Limbic Cortex Hypothalamus Thalamus

Periaqueductal gray HT-5

Enkephelin

LC Noradrenergic neurons

Medullary raph nucleus

Dorsal horn Periphery

P – NOCICEPTIVE PATHWAY – AFFERENT FIBERS Pain

Fibers

Nociceptors

Aδ-myelinated

mechanical

sharp, pricking pain

)2-5μm(

thermal-mechanical

burning pain

C-unmyelinated

thermal-mechanical

freezing pain

)0.2-1.5 μm(

Polymodul )mechanical, chemical and thermal(

slow burning pain

Conduction velocity m/s 5-30

0.5-2 m/s

P – NOCICEPTIVE PATHWAY – CHEMICAL MEDIATORS

• • • •

Bradykinin PG, Leukotrienes Tissue lesion K +, H + Serotonin, histamine, substance-P platelets

mast cells nerve ending

P – NOCICEPTIVE PATHWAY – CHEMICAL MEDIATORS platelets

serotonin

Mast cells

,Mechanical ,thermal chemical lesion

CGRP Substance P Dorsal horn Ganglion neuron

Histamine Bradykinin K+-H+ Prostaglandins

Primary afferent nociceptor CGRP Substance P Spinal cord

Blood vessel

Bradykinin receptor

Icatibart

Gq PLC Excitation

PI

+

DAG, IP3

H

Anandamide PKC Heat > 450C

VR1 VR1 cationic channels

Ca+2 influx

• Depolarization • Substance P • CGRP

NOCICEPTIVE PATHWAY – CNS • Spinal cord circuitry – Ascending neuron pathway • Dorsal horn – neurotransmitters and receptors • Brain centers and pain perception

Sometholic association cortex )perception and meaning( Primary somatosensory cortex )discrimination, location and intensity (

Paleospinothalamic pathway )dull aching pain(

Neospinothalamic tract )sharp, bright pain(

Thalamus )Sensation( VPL ILN

Spinal cord and dorsal horn Pain modulating circuits C-fiber )slow(

Aδ )fast(

Nociceptive stimuli

Limbic cortex )emotional experience (

Dorsal horn neuron

Nk-1 CGRP-R AMPA-R NMDA-R

Substance P

CGRP

pe ri

ph era ln fib ocic ers ep tiv e

Glutamate

DORSAL HORN – NEUROTRANSMITTERS / RECEPTORS

• Glutamate – fast EPSP • Substance P – slow EPSP • Glutamate – confine • Substance P – Diffuse

ENDOGENOUS ANALGESIC MECHANISMS

• Opioid and related peptides • Descending analgesic pathway

OPIOD PEPTIDES • Endorphin – μ, δ receptors • Met/Leu-enkephilin – δ, μ, κ • Dynorphin – κ, μ, δ

OPIOD PEPTIDES • μ – Analgesia, respiratory depression, physical dependence, eupohoria • δ – Analgesia (spinal), respiratory depression • κ – Analgesia (peripheral), dysphoria, physical dependence (low)

DESCENDING CONTROL PATHWAY Limbic Cortex Hypothalamus Thalamus

Periaqueductal gray HT-5

Enkephelin

LC Noradrenergic neurons

Medullary raph nucleus

Dorsal horn Periphery