Anda di halaman 1dari 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

Pain occurs with different degrees of severity


Mild pain:
Does not interfere noticeably with everyday life

Moderate pain:
Severe chronic pain:

May cause some annoyance and perceived as unpleasant

Affects a persons 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 persons 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 persons 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 elses pain Ren Leriche, French surgeon, 18791955

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 Fast pain slow pain Viscera pain Referred pain Non-nocicieptor pain Inflamatory Neuropathic pain Central neuropathic pain

Lesions to nerves or cns

Muscle 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)

Viscoelastic tone (specific tone)

Contractile activity

Elastic stiffness

Viscoelastic stiffness

Contracture (no EMG 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 DRG C fiber Ad fiber DRG Time

Second pain

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

Spinothalamic tract
Dorsal thalamus

Association cortex SI cortex

Ventral thalamus

PAG

Brainstem reticular formation

Spinothalamic tract DRG Receptor Dorsal horn

Midline

Cortex
Association cortex SI cortex

Nonspecific (dorsal) thalamic nuclei

Dorsal thalamus Ventral thalamus

PAG

Reticular formation Brain stem Trigeminal nerve Anterolateral funiculus

Brainstem reticular formation

Spinal cord
Spinothalamic tract DRG Receptor Dorsal horn

Spinal nerves

Cerebral cortex Thalamus

Trigeminal ganglion Midbrain

Motor nuclei RF

Brainstem

Spinalcord

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 (contralat.) SII (ipsilateral)

Projection of unmyelinated C fibers. Notice: Projection to SII is bilateral but only the SI receives input from C fibers

VPI VMpo

Lateral portion of STT

I II

DRG

Midline

Association cortex SI cortex

Spinoreticular tract

Dorsal thalamus

Reticular formation of pons

DRG Receptor Dorsal horn

Reticular formation of melulla

Midline

Spinomesencephalic tract
Hypothalamusamygdala limbic system

Periaqueductal gray PAG

DRG Receptor Dorsal horn

Limbic system SMP Prefrontal cortex

Association cortex

SII

"WHAT"
Dorsal thalamus Ventral thalamus

SI cortex

Pathways involved in mediating the sensation of nociceptor pain

"WHERE"

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 Post synaptic inhibition Presynaptic inhibition Lamina II interneuron

Nociceptor fiber DRG

Forebrain Forebrain NST

Thalamus

Innervation by the vagus nerve of organs in the lower abdomen involving the nucleus of the solitary tract (NST)
Spinal pain neuron

NA-serotonin pathway

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.
afferents

Spinal cord
T11 -L4

DRG Viceral afferents

S 3-S 4

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)

Thalamus Nocieptive dorsal horn neuron

From nociceptor DRG

Spinothalamic tract activate dorsomedial thalamus

STT

Reticular formation Dorsomedial thalamus

Association cotices

PAG Hypothalamus Amygdala

Cingulate gyrus

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
50 40 30 20 10 0
7.53 (0.36) 3.83 (0.94) 6.08 (1.08) 46.21 (5.92) 45.59 (8.06)

Trigger point Adjacent non-tender muscle

4.84 (0.52)

Normal subjects N=8

Tension headache patients N=29

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
Chronic excitation of visceral and deep somatic afferents Trauma with/without peripheral nerve lesion ABNORMAL STATE OF AFFERENT NEURONS DISTORTED INFORMATION P ROCESSING IN SP INAL CORD Abnormal regualation of blood flow and sweating MOVEMENT DISORDERS ABNORMAL ACTIVITY IN MOTONEURONS TO SKELETAL MUSCLE ABNORMAL SYMP ATHETIC ACTIVITY (VASO-SUDOMOTOR ORTHER ABNORMALITIES? Sympathetic block

Central lesion

P ain

CRPS: Complex regional pain syndrome

Swelling Trophic 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: Mller and Pinkerton, 1997

Temporal integration during development of carpal tunnel syndrome

From: Mller and Pinkerton, 1997

Hyperalgesia from experimentally induced burns

B
Before burn After burn
14 12 10 8 6 4

Mechanical hyperalgesia Flare

C A B D 2

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: Mller: Sensory Systems, 2002

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


40

Control NMDA antagonist

30

20

10

0 0 10 Stimulus number 20

Severe neuropathic pain affects a persons 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: Mller: 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 persons 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: Mller: Sensory Systems, 2003

Connections from a sensory system to the amygdala the low route

From: Mller: Sensory Systems, 2003

The amygdala is involved in fear and other mood disorders

Connections from the amygdala

From: Mller: 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