pain and its woes

7/29/2019 PAIN and its WOES

1/97

Pain is subjective

Self-experience

Experience depends on circumstances

Pain can cause many different reactions: Activate autonomic system (heart rate, blood

pressure, sweating, etc.)

Muscle activity

Mood (fear, anxiety, depression) Prevent sleep


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Pain occurs with different

degrees of severity Mild pain:Does not interfere noticeably with everyday life

Moderate pain:May cause some annoyance and perceived as unpleasant

Severe chronic pain:Affects a persons entire life in major ways


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There are many forms of pain

Mild pain:

Does not interfere noticeably with everydaylife

Moderate pain:

May cause some annoyance and may be

perceived as unpleasant

Severe pain:

Affects a persons entire life in major ways


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Different forms of pain

Acute pain

Chronic pain

Somatic pain Neuropathic pain

Central neuropathic pain


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Pain has many different forms,but the same name

Tinnitus has many differentforms but the same name


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There are different types ofpain

Somatic and visceral pain (Stimulation ofnociceptors)

Pain ceases when stimulation ceases

Neuropathic pain

Pain is related to the nervous system


Plastic changes in the function of the CNS May be persistent


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It is important to have differentnames for for different

disorders

We cannot think about matters that do not

have names

The same words is used to describe verydifferent forms of tinnitus and pain

Using the same names for fundamentallydifferent disorders is a disadvantage instudying and treating such disorders


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Severe pain affects a persons

entire life in major ways

Prevent or disturb sleep

Interfere with or prevents intellectual work May cause suicide

May involve limbic structures causing affectivereactions

Often accompanied by abnormal sensations fromtouch


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How prevalent is severe

pain?

Some pain was reported by 86% of

individuals above the age of 65(Iowa study, 1994)

The prevalence of severe pain was 33% for

people at age 77 and above (Swedishstudy, 1996)


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How prevalent is severe

pain?

Some pain was reported by 86% of

individuals above the age of 65(Iowa study, 1994)

The prevalence of severe pain was 33% for

people at age 77 and above (Swedishstudy, 1996)


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Pain

The only tolerable pain is someone elses pain

Ren Leriche, French surgeon, 18791955


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There are different types of

pain

Somatic and visceral pain (Stimulationof nociceptors)

Pain ceases when stimulation ceases

Neuropathic pain

Pain is related to the nervous system


Plastic changes in the function of the CNS

May be persistent


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Pain

Non-nocicieptorpain

Stimulation ofnociceptors

Muscle pain

Somaticpain

Viscerapain

Fast pain

slow pain

Referred

pain

Lesions to

nerves orcns

Central

neuropathicpain

Inflamatory Neuropathicpain


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Central neuropathic pain:

Pain sensation caused by abnormal neural activityin the CNS

Hyperacusis:

Sounds are perceived louder than normal

Allodynia:

Sensation of pain from normally innocuousstimulation (such as light touch)

Hyperpathia:

Exaggerated and prolonged reactions to painfulstimuli


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Somatic and visceral pain

(Stimulation of nociceptors)

Burning (temperature) Injury

Inflammation

Chemicals

Compression of spinal nerve roots (nervi nervorum)


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Muscle pain


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MUSCLE TONE(general tone)

Contractileactivity

Viscoelastic tone(specific tone)

Electrogenicspasm

(pathological)

Contracture(no EMGactivity)

Electrogeniccontraction

(normal)

Viscoelasticstiffness

Elasticstiffness

Relationship between commonly used terms to characterize

muscle tension:

Tone, stiffness, contracture, and spasm


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Tension type headaches

with trigger zones in

the temporalis muscle (

),in suboccipital,

sternocleidomastoid

and upper trapezius

muscles (), from where

pain attacks can be elicited


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Neuropathic pain

Pain of the nervous system

Neuralgias

Anesthesia dolorosa

Root pain

Stroke pain


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Neuropathic pain

All pain of neural origin

The term is mostly used by neurologistsfor pain caused by disorders of peripheral

nerves and cranial nerves


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Normal Neuropathic


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(WDR neurons, thalamus)


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Acute pain may promote

development of central neuropathic

pain

Central neuropathic pain is a neurologicdisorder


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Acute pain sensation may not

be a sign of pathology

Pain sensation can be elicited by: Stimulation of nociceptors

Overstimulation of other receptors


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Acute pain has two phases:

A fast (sharp) and a slow

(burning) sensation

The slow and delayed pain is mediatedby unmyelinated fibers (C-fibers).

The fast phase is mediated by

myelinated fibers (A).


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Time

Time

Time

First pain Second pain

X

X

C fiber

DRG

DRG

DRG

DRG

DRG

DRG

Ad fiber


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Fast and slow pain are different

Fast pain (stinging):

Well defined with regards to location Its strength is defined

Slow pain (aching):

Diffuse, poorly localized anatomically Difficult the estimate its strength


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Different types

of nerve fibers

carry differentkinds of pain


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Temperature

There are four different temperature

receptors:

Cool and warmth (sensory receptors)

Cold and heat (nociceptors)


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Temperature

1. Cool and warmth receptors mediate sensation oftemperature

2. Cold and heat receptors are nociceptors that mediatesensation of pain.

3. Cool and warmth receptors are innervated by smallmyelinated (A fibers, diameter 1-5 m, conductionvelocity 5-30 m/sec).

4. Cold and heat receptor are innervated by unmyelinatedfibers (C-fibers, diameter 0.2-2 m; conduction velocity

0.5-1 m/sec).


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DRG

Receptors


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Wid d i


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Wide dynamic

range neuron


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THE ANTERIOR LATERALSYSTEM MEDIATES PAIN

SENSATIONS

The spinothalamic tract is the best

known of the anteriorlateral tracts

A i iMidline


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Brainstemreticular

formation

Ventralthalamus

PAG

DRG

cortex

Association cort ex

Spinothalamictract

Dorsal

thalamus

DorsalhornReceptor

SI

Spinothalamic tract

Nonspecific (dorsal)C


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Spinal

nerves

Anterolateralfuniculus

Trigeminalnerve

Reticularformation

p ( )thalamic nucleiCortex

Brain stem

Spinalcord

Brainstemreticular

formation

Ventralthalamus

PAG

DRG

cortex

Association cortex

Spinothalamictract

Dorsalthalamus

Midline

DorsalhornReceptor

SI


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Trigeminalganglion

Thalamus

Cerebralcortex

Motornuclei

RFBrainstem

Midbrain

Spinalcord

SIMIDLINEAscending projections of


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I

II

SII

VPL

VPI

Brainstem

Anteriror portionof STT

MIDLINEAscending projections of

the anteriorportion

of the STT from neurons

in lamina IV-V of the

spinal horn.

VPI: Ventral posterior

inferior (nuclei of thalamus);

VPL: Ventral posteriorlateral (nuclei of thalamus);

SI: Primary

somatosensory cortex;

SII: secondary

somatosensory cortex

3 (SI)MIDLINE


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I

II

3a (SI)

Dorsal

Anterior

insulaVPI

VMpo

Brainstem

Thalamus

Area 24c

PAG

Lateral

portion

of STT

Projections of the

lateral portion of

the STT from cells

in lamina I of the

dorsal horn

MIDLINE


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SI (contralat.)

VPI

VMpo

SII (contralat.) SII

(ipsilateral)

Lateralportion

of STTDRG

I

II

Projection of

unmyelinated C fibers.

Notice: Projection

to SII is bilateral

but only the SI

receives input

from C fibers

AssociationMidli


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Reticularformationof melulla

Dorsalhorn

DRG

Receptor

Reticularformationof pons

cortex

AssociationcortexMidline

Dorsalthalamus

SI

Spinoreticular tract

Midline


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Dorsalhorn

DRG

Receptor

Periaqueductal grayPAG

Hypothalamus-amygdala

limbic system

Spinomesencephalic tract

Limbic system Association cortex


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Reticularformation

Ventral

thalamus

cortex

Prefrontal

cortex

SMP

AROUSAL

Anteriorlateral tract

Mediallemniscus

Dorsalthalamus

SII

"WHERE"

"WHAT"SI

Pathways involved

in mediating the

sensation ofnociceptor pain

Frontal lobe


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Hypothalamus

Amygdala

Locus coeruleus

Nucleus cuneiformis

Pontomedular

reticular

formation

DRG

Fromnociceptors

Dorsalhorn

RVM

PAG

Ascending

pain pathways

o ta obe

Input to the

periaquaductal gray

(PAG) and

pathways that modulate

transmission of painsignals by the PAG

through the rostral

ventromedial medulla

(RVM) pathway.


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Dorsolateralpontomesencephalic

tegmentum pathway (DLTP).DLPT

DRG

Fromnociceptors

Dorsalhorn

PAG

Ascending(crossed)

pain pathways

From rapheDescending pathways from raphe nucleus(NA t i th )


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NA serotoninpathway

DRG

Nociceptorfiber

Lamina Iinterneuron

Lamina II

interneuron

Presynapticinhibition

Post synapticinhibition

From raphenucleus

To thalamus

(NA-serotonin pathway)

Forebrain


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NA-serot oninpathway

Forebrain

Thalamus

Forebrain

Spinal

pain neuron

NST

Innervation by the

vagus nerve of organs

in the lower abdomen

involving the nucleus

of the solitary tract (NST)

DLF: Dorsolateral funiculus


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DLF: Dorsolateral funiculus

VLF: Ventrolateral funiculus

RVM: Rostroventral medulla

Vi l i i diff t f


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Visceral pain is different from

somatic pain

Inconsistent sensations

Sometimes referred pain to body surface

Often inescapable

Spinal cordVisceral afferent


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T11-L4

S3-S4

Viceralafferents

Uterus

Efferent

Nociceptors

Viceralafferents

DRG

DRG

Viceralafferents

Painfibers

Viceralreceptors

Bladder

Visceral afferent

innervation in the

lower body and

motor (efferent)innervation.

Thalamus


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PAG

RVM5HT

non 5HT

DLPTNE

non NE

Dorsalhorn

Primaryafferents

+ _

Two-way connections

between PAG, DLPT

and RVMand their connections

to the dorsal horn

The dual input to dorsal horn cells from RVM


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DRG

From

nociceptor

Off-neuron(Morphineexcites)

On-neuron

(Morphine inhibits)

Thalamus

Nocieptivedorsal

horn neuron

p

Spinothalamic tract activate dorsomedial thalamus


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Hypothalamus

Dorsomedialthalamus

PAG

STT

Amygdala

Associationcotices

Reticularformation

Cingulate

gyrus

Hypothesis about expansion of receptive field and creation oft i i t b ki f d t


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Corticalreceptivefield

Cerebral cortex

Cortex

Spinal cord

DRG

Receptive fields

trigger points by unmasking of dormant synapses

Mean EMG amplitudes recorded from a muscle


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0

10

20

30

40

50

N=8

7.53(0.36) 3.83

(0.94)

46.21(5.92)

6.08(1.08)

45.59(8.06)

4.84(0.52)

Trigger point

Adjacentnon-tendermuscle

N=29 N=25

Normalsubjects

Tensionheadachepatients

Fibromyalgiapatients

Mean EMG amplitudes recorded from a muscle

at a trigger point and at an adjacent

non-tender muscle


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Itch

The basis of itching is poorly understood

but it has similarities with pain.

CENTRAL NEUROPATHIC


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CENTRAL NEUROPATHIC

PAIN MAY INVOLVE THE

SYMPATHETIC NERVOUS

SYSTEM

REFLEX SYMPATHETIC

DYSTROPHY, RSD

Role of sympathetic nervous


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Role of sympathetic nervous

system

in neuropathic pain

1. Sympathetic system is activated by stimulation ofpain fibers

2. Sympathetic fibers secrete nor-epinephrine nearmechanoreceptors

3. Sensitivity of mechanoreceptors increases

4. Activation of sympathetic system increases5. Result: A viscous circle that causes RSD

Increased activity


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Increased activity

Activation of the

sympatheticnervous system

Nociceptorsensitization

Liberation of noradrenalin

Trauma causeactivation of pain


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activation of pain

fibers (C-fibers),

which sensitize WDR

neurons

Sensitized WDR

neurons cause

pressure to activate

pain circuits

(allodynia)

Mechanoreceptors are

activated by

epinephrine that is

secreted from

sympathetic nerves in

absence of mechanical

stimulation

Contemporary hypotheses of neural mechanisms involved

i ti CRPS I d II f ll i t


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Chronic excitation of

visceral and deep

somatic afferents

Abnormal

regualation of blood

flow and sweating

Swelling

Trophic changes

Trauma with/ without

peripheral

nerve lesion

Pain

MOVEMENT

DISORDERS

ABNORMAL

ACTIVITY INMOTONEURONS

TO SKELETAL

MUSCLE

ABNORMAL

SYMPATHETICACTIVITY

(VASO-SUDOMOTOR

ORTHER

ABNORMALITIES?

ABNORMAL STATE OF

AFFERENT NEURONSSympathetic

block

Central lesion

DISTORTED

INFORMATIONPROCESSING IN

SPINAL CORD

in generating CRPS I and II following trauma

CRPS: Complex regional pain syndrome


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Neuropathic pain

Pain of the nervous system

Neuralgias

Anesthesia dolorosa

Root pain

Stroke pain



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(WDR neurons, thalamus)


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All pain of neural origin

The term is mostly used for pain

caused by disorders of peripheral nerves

and cranial nerves

Central neuropathic pain may


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be caused by:

Chronic inflammation

Sensitization of skin receptors

Changes in the connectivity of the CNS

(through neural plasticity)



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development of central neuropathic

pain

Central neuropathic pain is a neurologicdisorder

Wide dynamic


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range neurons


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develop from peripheral nerveinjuries

The pain is referred to the peripheral

location

Treatment of that location will not help

The patient and the surgeon are both

frustrated

C t l thi i


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involve changes in function

Normally innocuous stimulation

becomes painful (allodynia)

Stimuli that normally cause mild pain

cause an exaggerated reaction

(hyperpathia)

Central neuropathic pain is


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Central neuropathic pain is

often accompanied by altered

perception of touch and painstimuli

Touch may cause pain (allodynia)

Increased sensitivity to pain

(hyperalgesia) Painful stimulation may cause

exaggerated reaction to pain and

prolonged pain (hyperpathia)



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involve changes in function

Normally innocuous stimulation

becomes painful (allodynia)

Stimuli that normally cause mild paincause an exaggerated reaction

(hyperpathia)

All d i P i f ll


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Allodynia: Pain from normally

innocuous stimulation (of the skin)

Hyperalgesia: Extreme sensitiveness

to painful stimuli.

Hyperpathia: Exaggerated subjective

response to painful stimuli, with acontinuing sensation of pain after the

stimulation has ceased.

Temporal integration


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Neuropathic painNormal

From: Mller and Pinkerton, 1997

Pain

Tingling

Temporal integration during development of


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A B

carpal tunnel syndrome

From: Mller and Pinkerton, 1997

Hyperalgesia from experimentally induced burns


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Site A Site B Site C

2

4

6

8

10

12

14

1 cm

Before burn

After burn

C

A

B

D

Mechanical

hyperalgesia

Flare

BA

Hypothesis for referred pain andsensitization of different nociceptors


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p

S iti ti


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Sensitization

Peripherally:

Receptors

Centrally

Increased synaptic efficacy

Expression of new neurotransmitters

Neuromodulators

Morphological re-organization

Oth h i t d


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From: Mller: Sensory Systems, 2002

Wind-up

Response to second stimulus is stronger than

the response to the first one

Change in temporal integration

Other phenomena associated

with chronic pain

"Wind-up" is NMDA mediated.Response with and without an NMDA antagonist.


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40

30

20

10

0

0 10 20

ControlNMDA antagonist

Stimulus number

p g

S thi i


84/97

Severe neuropathic pain

affects a persons entire life inmajor ways


Interfere with or prevent

Intellectual work

Involve limbic structures causing affectivereactions


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How do we explain these

symptoms and signsphysiologically and

anatomically?Where is the neural activity that

give a sensation of pain

generated?

The anatomical location of the


86/97

abnormality that cause pain may be

different from that to which the painis referred

Referred pain


The abnormal neural activity that


87/97

The abnormal neural activity that

causes symptoms are not

generated at the location where

the symptoms are felt

Example:

Posttraumatic central neuropathic pain

Phantom pain

Central pain pathways for pain


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Central pain pathways for pain

PROJECT TO PRIMARY CORTICESWITH SPATIAL INFORMATION

(WHERE) PROJECT OBJECTIVE INFORMATION

(WHAT) TO MANY DIFFERENT PARTS

OF THE CNS. NON-CLASSICAL PATHWAYS ALSO

CONTRIBUTES TO AROUSAL


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SUMMARY OF PATHWAYS

INVOLVED IN MEDIATING

THE SENSATION OF PAIN

CENTRAL PAIN PATHWAYS

PROJECT TO PRIMARY

CORTICES WITH SPATIAL

INFORMATION (WHERE)

OBJECTIVE INFORMATION

(WHAT) TO MANY

DIFFERENT PARTS OF THE

CNS (FOR EXAMPLE THE

AMYGDALA)

NON-CLASSICAL

INFORMATION ALSO

CONTRIBUTES TO

AROUSAL


R l f l l ti it


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Reversal of neural plasticity

TENS (transderm electric nervestimulation) has been used for many years

in treatment of chronic pain

Recently, sound stimulation in various

forms have been introduced in treatment

of severe tinnitus

S thi i


91/97

Severe neuropathic pain

affects a persons entire life inmajor ways


Interfere with or prevent

Intellectual work

Involve limbic structures causing affectivereactions

How can pain information reach


92/97

p

the amygdala?

Through the thalamus

Through routes that are enhanced by

expression of neural plasticity (re-routingof information)

Connections from a sensory system to the amygdala

the high route


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the high route

Connections from a sensory system to the amygdala

the low route


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the low route


The amygdala is involved in fear


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yg

and other mood disorders

Connections from the amygdala


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INESCAPABLEPAIN

INVOLVES OTHER PARTSOF THE CNS THAN

ESCAPABLE PAINActivate different columns in the

PAG coordinating either active of

passive coping

pain and its woes

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