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
 Third order
Brain neuron
)Thalamus(

Second order
Spinal Cord neuron
)Dorsal horn(

Receptor

First-order neuron
)Dorsal root ganglion(
 DESCENDING CONTROL PATHWAY

Limbic Cortex

Hypothalamus

Thalamus Periaqueductal gray

LC
HT-5 Enkephelin Noradrenergic neurons

Medullary raph nucleus

Dorsal horn

Periphery
P – NOCICEPTIVE PATHWAY – AFFERENT FIBERS

Fibers Nociceptors Pain Conduction

velocity
Aδ-myelinated mechanical sharp, pricking pain
m/s 5-30
)2-5μm( thermal-mechanical burning pain

C-unmyelinated thermal-mechanical freezing pain 0.5-2 m/s

)0.2-1.5 μm( Polymodul slow burning pain

)mechanical,
chemical
and thermal(
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
,Mechanical Mast cells
,thermal
chemical CGRP
Substance P
lesion

Histamine Dorsal horn

Ganglion neuron

Bradykinin
K+-H+
Prostaglandins
Primary afferent
nociceptor

CGRP
Substance P

Spinal cord
Blood vessel
 Bradykinin receptor Icatibart

Gq

PLC

PI Excitation

+
H DAG, IP3

Anandamide
PKC
Heat > 450C VR1

VR1 cationic channels • Depolarization

• Substance P
• CGRP

Ca+2
influx
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 (

Thalamus )Sensation( Limbic cortex

VPL ILN )emotional experience (

Paleospinothalamic
)sharp, bright pain(

)dull aching pain(

Neospinothalamic

pathway
tract

Spinal cord and dorsal horn

Pain modulating circuits
C-fiber Aδ
)slow( )fast(

Nociceptive stimuli
 Dorsal horn neuron

Nk-1

CGRP-R
AMPA-R
NMDA-R

CGRP Substance P

Glutamate
e
tiv
ers ep
fib ocic
ln
era
ph
ri
pe
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

LC
HT-5 Enkephelin Noradrenergic neurons

Medullary raph nucleus

Dorsal horn

Periphery