Transcript SENSORY SYSTEMS

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
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 person’s entire life in major ways
There are many forms of pain
•
Mild pain:
Does not interfere noticeably with everyday
life
• Moderate pain:
May cause some annoyance and may be
perceived as unpleasant
• Severe pain:
Affects a person’s entire life in major ways
Different forms of pain
•
•
•
•
•
Acute pain
Chronic pain
Somatic pain
Neuropathic pain
Central neuropathic pain
Pain has many different forms,
but the same name
Tinnitus has many different
forms but the same name
There are different types of
pain
•
Somatic and visceral pain (Stimulation of
nociceptors)
– Pain ceases when stimulation ceases
• Neuropathic pain
– Pain is related to the nervous system
• Central neuropathic pain
– Plastic changes in the function of the CNS
– May be persistent
It is important to have different
names for for different
disorders
• We cannot think about matters that do not
have names
• The same words is used to describe very
different forms of tinnitus and pain
• Using the same names for fundamentally
different disorders is a disadvantage in
studying and treating such disorders
Severe pain affects a person’s
entire life in major ways
•
•
•
Prevent or disturb sleep
Interfere with or prevents intellectual work
May cause suicide
May involve limbic structures causing affective
reactions
Often accompanied by abnormal sensations from
touch
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 (Swedish
study, 1996)
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 (Swedish
study, 1996)
Pain
“The only tolerable pain is someone else’s pain”
René Leriche, French surgeon, 1879–1955
There are different types of
pain
• Somatic and visceral pain (Stimulation
of nociceptors)
– Pain ceases when stimulation ceases
• Neuropathic pain
– Pain is related to the nervous system
• Central neuropathic pain
– Plastic changes in the function of the CNS
– May be persistent
Pain
Stimulation of
nociceptors
Somatic
pain
Viscera
pain
Fast pain
slow pain
Referred
pain
Muscle pain
Non-nocicieptor
pain
Inflamatory
Neuropathic
pain
Lesions to
nerves or
cns
Central
neuropathic
pain
• Central neuropathic pain:
– Pain sensation caused by abnormal neural activity
in the CNS
• Hyperacusis:
– Sounds are perceived louder than normal
• Allodynia:
– Sensation of pain from normally innocuous
stimulation (such as light touch)
• Hyperpathia:
– Exaggerated and prolonged reactions to painful
stimuli
Somatic and visceral pain
(Stimulation of nociceptors)
•
•
•
•
•
Burning (temperature)
Injury
Inflammation
Chemicals
Compression of spinal nerve roots (nervi nervorum)
Muscle pain
Relationship between commonly used terms to characterize
muscle tension:
Tone, stiffness, contracture, and spasm
MUSCLE TONE
(general tone)
Contractile
activity
Viscoelastic tone
(specific tone)
Elastic
stiffness
Viscoelastic
stiffness
Contracture
(no EM G
activity)
Electrogenic
spasm
(pathological)
Electrogenic
contraction
(normal)
Tension type headaches
with trigger zones in
the temporalis muscle (),
in suboccipital,
sternocleidomastoid
and upper trapezius
muscles (), from where
pain attacks can be elicited
  



Neuropathic pain
•
•
•
•
•
Pain of the nervous system
Neuralgias
Anesthesia dolorosa
Root pain
Stroke pain
Neuropathic pain
• All pain of neural origin
The term is mostly used by neurologists
for pain caused by disorders of peripheral
nerves and cranial nerves
Normal
Neuropathic
Central neuropathic pain
• Plastic changes in the function of the CNS
(WDR neurons, thalamus)
Acute pain may promote
development of central neuropathic
pain
• Central neuropathic pain is a neurologic
disorder
Acute pain sensation may not
be a sign of pathology
•
•
Pain sensation can be elicited by:
Stimulation of nociceptors
Overstimulation of other receptors
Acute pain has two phases:
A fast (sharp) and a slow
(burning) sensation
• The slow and delayed pain is mediated
by unmyelinated fibers (C-fibers).
• The fast phase is mediated by
myelinated fibers (A).
First pain
Second pain
DRG
C fiber
Ad fiber
DRG
Time
DRG
X
DRG
Time
DRG
X
DRG
Time
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
Different types
of nerve fibers
carry different
kinds of pain
Temperature
There are four different temperature
receptors:
Cool and warmth (sensory receptors)
Cold and heat (nociceptors)
Temperature
1.
2.
3.
4.
Cool and warmth receptors mediate sensation of
temperature
Cold and heat receptors are nociceptors that mediate
sensation of pain.
Cool and warmth receptors are innervated by small
myelinated (A fibers, diameter 1-5 m, conduction
velocity 5-30 m/sec).
Cold and heat receptor are innervated by unmyelinated
fibers (C-fibers, diameter 0.2-2 m; conduction velocity
0.5-1 m/sec).
Receptors
DRG
Wide dynamic
range neuron
THE ANTERIOR LATERAL
SYSTEM MEDIATES PAIN
SENSATIONS
The spinothalamic tract is the best
known of the anteriorlateral tracts
Midline
Association cortex
Spinothalamic tract
SI cortex
Dorsal
thalamus
Ventral
thalamus
PAG
Brainstem
reticular
formation
Spinothalamic
tract
DRG
Receptor
Dorsal
horn
Cortex
Midline
Association cortex
Nonspecific (dorsal)
thalamic nuclei
SI cortex
Dorsal
thalamus
Ventral
thalamus
Reticular
formation
PAG
Brain stem
Anterolateral
funiculus
Brainstem
reticular
formation
Spinal
cord
Spinothalamic
tract
DRG
Receptor
Dorsal
horn
Trigeminal
nerve
Spinal
nerves
Cerebral
cortex
Thalamus
Trigeminal
ganglion
Midbrain
Motor
nuclei
RF
Spinalcord
Brainstem
Ascending projections of
the anterior portion
of the STT from neurons
in lamina IV-V of the
spinal horn.
VPI: Ventral posterior
inferior (nuclei of thalamus);
VPL: Ventral posterior
lateral (nuclei of thalamus);
SI: Primary
somatosensory cortex;
SII: secondary
somatosensory cortex
SI
MIDLINE
VPL
SII
VPI
Brainstem
I
II
Anteriror portion
of STT
MIDLINE
3a (SI)
Projections of the
lateral portion of
the STT from cells
in lamina I of the
dorsal horn
Area 24c
Thalamus
VPI
VMpo
Dorsal
Anterior
insula
PAG
Brainstem
Lateral
portion
of STT
I
II
MIDLINE
SI (contralat.)
SII
(ipsilateral)
SII (contralat.)
Projection of
unmyelinated C fibers.
VPI
VMpo
Notice: Projection
to SII is bilateral
but only the SI
receives input
from C fibers
Lateral
portion
of STT
I
II
DRG
Association
cortex
Midline
Spinoreticular tract
SI cortex
Dorsal
thalamus
Reticular
formation
of pons
Reticular
formation
of melulla
DRG
Receptor
Dorsal
horn
Midline
Spinomesencephalic tract
Hypothalamusamygdala
limbic system
Periaqueductal gray
PAG
DRG
Receptor
Dorsal
horn
Limbic system
Association cortex
SMP
Prefrontal
cortex
Pathways involved
in mediating the
sensation of
nociceptor pain
SII
"WHAT"
SI cortex
Dorsal
thalamus
"WHERE"
Ventral
thalamus
Medial
lemniscus
Reticular
formation
AROUSAL
Anterior
lateral tract
Frontal lobe
Amygdala
Input to the
Hypothalamus
periaquaductal gray
(PAG) and
pathways that modulate
transmission of pain
signals by the PAG
through the rostral
ventromedial medulla
(RVM) pathway.
Locus coeruleus
PAG
Nucleus cuneiformis
Pontomedular
reticular
formation
RVM
From
nociceptors
Ascending
pain pathways
DRG
Dorsal
horn
PAG
Dorsolateral
pontomesencephalic
tegmentum pathway (DLTP).
DLPT
From
nociceptors
Ascending
(crossed)
pain pathways
Dorsal
horn
DRG
Descending pathways from raphe nucleus
From raphe
(NA-serotonin pathway)
nucleus
To thalamus
NA serotonin
pathway
Lamina I
interneuron
Nociceptor
fiber
Post synaptic
inhibition
DRG
Presynaptic
inhibition
Lamina II
interneuron
Forebrain
Forebrain
NST
Thalamus
Innervation by the
vagus nerve of organs
in the lower abdomen
involving the nucleus
of the solitary tract (NST)
NA-serotonin
pathway
Spinal
pain neuron
DLF: Dorsolateral funiculus
VLF: Ventrolateral funiculus
RVM: Rostroventral medulla
Visceral pain is different from
somatic pain
• Inconsistent sensations
• Sometimes referred pain to body surface
• Often inescapable
Visceral afferent
innervation in the
DRG
lower body and
motor (efferent)
Viceral
innervation.
Spinal cord
T11-L4
Viceral
afferents
afferents
S 3-S 4
DRG
Viceral
afferents
Uterus
Efferent
Viceral
receptors
Pain
fibers
Bladder
Nociceptors
Thalamus
Two-way connections
between PAG, DLPT
and RVM
and their connections
to the dorsal horn
PAG
DLPT
NE
non NE
RVM
5HT
non 5HT
_
+
Dorsal
horn
Primary
afferents
The dual input to dorsal horn cells from RVM
On-neuron
(Morphine inhibits)
Off-neuron
(Morphine
excites)
From
nociceptor
Thalamus
Nocieptive
dorsal
horn neuron
DRG
Spinothalamic tract activate dorsomedial thalamus
STT
Reticular
formation
Dorsomedial
thalamus
Association
cotices
Cingulate
gyrus
PAG
Hypothalamus
Amygdala
Hypothesis about expansion of receptive field and creation of
trigger points by unmasking of dormant synapses
Cerebral cortex
Cortical
receptive
field
Cortex
Spinal cord
DRG
Receptive fields
Mean EMG amplitudes recorded from a muscle
at a trigger point and at an adjacent
non-tender muscle
46.21
(5.92)
50
T rigger point
Adjacent
non-tender
muscle
45.59
(8.06)
40
30
20
10
0
7.53
(0.36) 3.83
(0.94)
Normal
subjects
N=8
6.08
(1.08)
T ension
headache
patients
N=29
4.84
(0.52)
Fibromyalgia
patients
N=25
Itch
• The basis of itching is poorly understood
but it has similarities with pain.
CENTRAL NEUROPATHIC
PAIN MAY INVOLVE THE
SYMPATHETIC NERVOUS
SYSTEM
• REFLEX SYMPATHETIC DYSTROPHY,
RSD
Role of sympathetic nervous
system
in neuropathic pain
1. Sympathetic system is activated by stimulation of
pain fibers
2. Sympathetic fibers secrete nor-epinephrine near
mechanoreceptors
3. Sensitivity of mechanoreceptors increases
4. Activation of sympathetic system increases
5. Result: A viscous circle that causes RSD
Increased activity
Activation of the
sympathetic
nervous system
Nociceptor
sensitization
Liberation of noradrenalin
Trauma cause
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
in generating CRPS I and II following trauma
Central lesion
Chronic excitation of
visceral and deep
somatic afferents
T rauma with/without
peripheral
nerve lesion
ABNORMAL ST AT E OF
AFFERENT NEURONS
P ain
Sympathetic
block
DIST ORT ED
INFORMAT ION
P ROCESSING IN
SP INAL CORD
Abnormal
regualation of blood
flow and sweating
MOVEMENT
DISORDERS
ABNORMAL
ACT IVIT Y IN
MOT ONEURONS
T O SKELET AL
MUSCLE
ABNORMAL
SYMP AT HET IC
ACT IVIT Y
(VASO-SUDOMOT OR
ORT HER
ABNORMALIT IES?
CRPS: Complex regional pain syndrome
Swelling
T rophic changes
Neuropathic pain
•
•
•
•
•
Pain of the nervous system
Neuralgias
Anesthesia dolorosa
Root pain
Stroke pain
Central neuropathic pain
• Plastic changes in the function of the CNS
(WDR neurons, thalamus)
Central neuropathic pain
• 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
be caused by:
•
•
•
Chronic inflammation
Sensitization of skin receptors
Changes in the connectivity of the CNS
(through neural plasticity)
Acute pain may promote
development of central neuropathic
pain
• Central neuropathic pain is a neurologic
disorder
Wide dynamic
range neurons
Central neuropathic pain may
develop from peripheral nerve
injuries
• The pain is referred to the peripheral
location
• Treatment of that location will not help
• The patient and the surgeon are both
frustrated
Central neuropathic pain may
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
often accompanied by altered
perception of touch and pain
stimuli
• Touch may cause pain (allodynia)
• Increased sensitivity to pain
(hyperalgesia)
• Painful stimulation may cause
exaggerated reaction to pain and
prolonged pain (hyperpathia)
Central neuropathic pain may
involve changes in function
•
•
Normally innocuous stimulation
becomes painful (allodynia)
Stimuli that normally cause mild pain
cause an exaggerated reaction
(hyperpathia)
Allodynia: Pain from normally
innocuous stimulation (of the skin)
Hyperalgesia: Extreme sensitiveness
to painful stimuli.
Hyperpathia: Exaggerated subjective
response to painful stimuli, with a
continuing sensation of pain after the
stimulation has ceased.
Temporal integration
Normal
Neuropathic pain
Pain
Tingling
From: Møller and Pinkerton, 1997
Temporal integration during development of
carpal tunnel syndrome
A
B
From: Møller and Pinkerton, 1997
Hyperalgesia from experimentally induced burns
B
A
Before burn
After burn
14
12
10
8
6
4
Mechanical
hyperalgesia
Flare
C
A
B
2
D
Site A
1 cm
Site B
Site C
Hypothesis for referred pain and
sensitization of different nociceptors
Sensitization
• Peripherally:
– Receptors
• Centrally
– Increased synaptic efficacy
– Expression of new neurotransmitters
– Neuromodulators
– Morphological re-organization
Other phenomena associated
with chronic pain
• “Wind-up”
– Response to second stimulus is stronger than
the response to the first one
• Change in temporal integration
From: Møller: Sensory Systems, 2002
"Wind-up" is NMDA mediated.
Response with and without an NMDA antagonist.
Control
NMDA antagonist
40
30
20
10
0
0
10
Stimulus number
20
Severe neuropathic pain
affects a person’s entire life in
major ways
•
•
•
Prevent or disturb sleep
Interfere with or prevent
Intellectual work
Involve limbic structures causing affective
reactions
How do we explain these
symptoms and signs
physiologically and
anatomically?
Where is the neural activity that
give a sensation of pain
generated?
The anatomical location of the
abnormality that cause pain may be
different from that to which the pain
is referred
• Referred pain
• Central neuropathic pain
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
• PROJECT TO PRIMARY CORTICES
WITH SPATIAL INFORMATION
(“WHERE”)
• PROJECT OBJECTIVE INFORMATION
(“WHAT”) TO MANY DIFFERENT PARTS
OF THE CNS.
• NON-CLASSICAL PATHWAYS ALSO
CONTRIBUTES TO AROUSAL
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
From: Møller: Sensory Systems, 2003
Reversal of neural plasticity
• “TENS” (transderm electric nerve
stimulation) 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
Severe neuropathic pain
affects a person’s entire life in
major ways
•
•
•
Prevent or disturb sleep
Interfere with or prevent
Intellectual work
Involve limbic structures causing affective
reactions
How can pain information reach
the amygdala?
• Through the thalamus
• Through routes that are enhanced by
expression of neural plasticity (re-routing
of information)
Connections from a sensory system to the amygdala
“the high route”
From: Møller: Sensory Systems, 2003
Connections from a sensory system to the amygdala
“the low route”
From: Møller: Sensory Systems, 2003
The amygdala is involved in fear
and other mood disorders
Connections from the amygdala
From: Møller: Sensory Systems, 2003
INESCAPABLE PAIN
INVOLVES OTHER PARTS
OF THE CNS THAN
ESCAPABLE PAIN
Activate different columns in the
PAG coordinating either active of
passive coping