Pain is subjective

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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 everyday life
• 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 different forms but the same
name 
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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

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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

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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 affective
  reactions
• Often accompanied by abnormal sensations from
  touch

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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 (Swedish study, 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 (Swedish study, 1996)

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Pain

• The only tolerable pain is someone elses pain
• René Leriche, French surgeon, 18791955

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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

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• 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

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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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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 neurologists for pain
  caused by disorders of peripheral nerves and
  cranial nerves

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Central neuropathic pain

• Plastic changes in the function of the CNS(WDR
  neurons, thalamus)

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Acute pain may promote development of central
neuropathic pain

• Central neuropathic pain is a neurologic disorder

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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 mediated by
  unmyelinated fibers (C-fibers).
• The fast phase is mediated by myelinated fibers
  (A?).

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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 different
kinds 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 of
   temperature
2. Cold and heat receptors are nociceptors that
   mediate sensation of pain.
3. Cool and warmth receptors are innervated by small
   myelinated (A? fibers, diameter 1-5 ?m,
   conduction velocity 5-30 m/sec).
4. Cold and heat receptor are innervated by
   unmyelinated fibers (C-fibers, diameter 0.2-2 ?m
   conduction velocity 0.5-1 m/sec).

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Wide dynamic range neuron
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THE ANTERIOR LATERAL SYSTEM MEDIATES PAIN
SENSATIONS

• The spinothalamic tract is the best known of the
  anteriorlateral tracts

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Spinothalamic tract
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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
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Projections of the lateral portion of the STT
from cells in lamina I of the dorsal horn
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Projection of unmyelinated C fibers. Notice
Projection to SII is bilateral but only the SI
receives input from C fibers
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Spinoreticular tract
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Spinomesencephalic tract
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Pathways involved in mediating the sensation of
nociceptor pain
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Input to the periaquaductal gray (PAG) and
pathways that modulate transmission of pain
signals by the PAG through the rostral
ventromedial medulla (RVM) pathway.
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Dorsolateral pontomesencephalic tegmentum
pathway (DLTP).
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Descending pathways from raphe nucleus
(NA-serotonin pathway)
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Innervation by the vagus nerve of organs in the
lower abdomen involving the nucleus of the
solitary tract (NST)
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DLF Dorsolateral funiculus VLF Ventrolateral
funiculus RVM Rostroventral medulla
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Visceral pain is different from somatic pain

• Inconsistent sensations
• Sometimes referred pain to body surface
• Often inescapable

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Visceral afferent innervation in the lower body
and motor (efferent) innervation.
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Two-way connections between PAG, DLPT and RVM
and their connections to the dorsal horn
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The dual input to dorsal horn cells from RVM
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Spinothalamic tract activate dorsomedial thalamus
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Hypothesis about expansion of receptive field and
creation of trigger points by unmasking of
dormant synapses
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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.

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CENTRAL NEUROPATHIC PAIN MAY INVOLVE THE
SYMPATHETIC NERVOUS SYSTEM

• REFLEX SYMPATHETIC DYSTROPHY, RSD

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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

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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
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Contemporary hypotheses of neural mechanisms
involved 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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Central neuropathic pain

• Plastic changes in the function of the CNS(WDR
  neurons, thalamus)

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Central neuropathic pain

• All pain of neural origin
• The term is mostly used for pain caused by
  disorders of peripheral nerves and cranial nerves

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Central neuropathic pain may be caused by

• Chronic inflammation
• Sensitization of skin receptors
• Changes in the connectivity of the CNS (through
  neural plasticity)

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Acute pain may promote development of central
neuropathic pain

• Central neuropathic pain is a neurologic disorder

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Wide dynamic range neurons
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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

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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)

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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)

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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)

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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 a continuing sensation of pain
after the stimulation has ceased.
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Temporal integration

Neuropathic pain
Normal
Pain
Tingling
From Møller and Pinkerton, 1997
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Temporal integration during development of
carpal tunnel syndrome
A
B
From Møller and Pinkerton, 1997
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Hyperalgesia from experimentally induced burns
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Hypothesis for referred pain and sensitization
of different nociceptors
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Sensitization

• Peripherally
• Receptors
• Centrally
• Increased synaptic efficacy
• Expression of new neurotransmitters
• Neuromodulators
• Morphological re-organization

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

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How do we explain these symptoms and signs
physiologically and anatomically?

• Where is the neural activity that give a
  sensation of pain generated?

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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

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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

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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

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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
From Møller Sensory Systems, 2003
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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

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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

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How can pain information reach the amygdala?

• Through the thalamus
• Through routes that are enhanced by expression of
  neural plasticity (re-routing of information)

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Connections from a sensory system to the
amygdala
the high route
From Møller Sensory Systems, 2003
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Connections from a sensory system to the
amygdala the low
route
From Møller Sensory Systems, 2003
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The amygdala is involved in fear and other mood
disorders
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Connections from the amygdala
From Møller Sensory Systems, 2003
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INESCAPABLE PAIN INVOLVES OTHER PARTS OF THE CNS
THAN ESCAPABLE PAIN

• Activate different columns in the PAG
  coordinating either active of passive coping