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Traumatic Brain Injury and Pain

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Title: Traumatic Brain Injury and Pain


1
Traumatic Brain Injury and Pain
  • F.Antonio Luque, M.D. Ph.D.
  • Neurology

2
Traumatic Brain Injury
  • TBI in the USA estimated 180-200 cases/100,000
  • Around 600,000 New TBI occur every year
  • 10 of these Injuries are fatal.
  • NIH survey estimates in USA 1.9 million suffer
    skull fracture or intracranial injury, ½ have
    suboptimal outcome.
  • Cost 40 Billion dollars/year

3
TRAUMATIC BRAIN INJURY
4
Military Fatalities By Time PeriodAs of 2/20/07
5
US Non Mortal Casualties Including non-hostile
and medical evacuations As of 2/3/07
6
Traumatic Brain Injury
  • Traumatic brain injury symptoms
  • Inability to find wordsInability to
    perform tasksConfabulating (putting unrelated
    bits of conversation into conversation
    gaps)ImpulsivityAgitationPoor judgment and
    poor insightSexual inappropriateness, including
    a lack of sexual inhibitionsFor more
    information, call (800) 877-VETS, or visit
    www.va.gov.

7
Frequency of PCS Symptoms following a MTBI
  • Poor concentration 71
  • Irritability 66
  • Tired a lot more 64
  • Depression 63
  • Memory problems 59
  • Headaches 59
  • Anxiety 58
  • Trouble thinking 57
  • Dizziness 52
  • Blurry or double vision 45
  • Sensitivity to bright light 40

Traumatic Brain Injury, VA Health Initiative
8
Causes of TBI (CDC Data)
  • Transportation (MVA) 48.9
  • Falls 25.8
  • Firearms 9.7
  • Other Assaults 7.5
  • Others 7.4
  • Unknown 0.6

Traumatic Brain Injury, VA Health Initiative
9
Severity Grades of TBI
  • Mild (Grade 1 ) altered or LOC normal CT or MRI, GCS 13-15, PTA
  • Moderate (Grade 2) LOC CT and/or MRI, GCS 9-12, PTA
  • Severe (Grade 3 4) LOC 6 hours with abnormal
    CT and/or MRI, GCS 7 days.

Traumatic Brain Injury VA Health Initiative
10
Functional Correlates of Injury Pathophysiology
  • Focal Cortical Contusion ground level fall,
    assault, gunshot wound. They can have
    Hemiparesis, aphasia, Seizures, visuoperceptual.
  • Diffuse Axonal Injury motor vehicle accident,
    non-ground level fall, geriatric ground level
    fall. They have confuse language, amnesia,
    apraxia, hypoarousal.
  • Hypoxic/Ischemic anoxia, cardiac arrest,
    prolonged elevated ICP. They have quadriparesis,
    spasticity, confusion, amnesia, hypoaraousal.

Traumatic Brain Injury VA Health Initiative
11
Frequency of PCS Symptoms following a MTBI
  • Poor concentration 71
  • Irritability 66
  • Tired a lot more 64
  • Depression 63
  • Memory problems 59
  • Headaches 59
  • Anxiety 58
  • Trouble thinking 57
  • Dizziness 52
  • Blurry or double vision 45
  • Sensitivity to bright light 40

Traumatic Brain Injury, VA Health Initiative
12
Specific or subjective PCS
  • Neurological or medical Headaches,
    Dizziness/vertigo, Tinnitus, blurred or double
    vision, light and or noise sensitivity, Nausea
    and vomiting, Fatigue, sleep disturbances,
    Physical weakness.
  • Cognitive Memory complaints, concentration
    complaints.
  • Psychological Irritability, Increase aggression,
    Depression, Anxiety.

Traumatic Brain Injury VA Health Initiative
13
Referrals ( Team work)
  • Audiologist
  • Kinesiotherapist
  • Neuro-ophthalmologist
  • Occupational therapist
  • Recreational therapist
  • Speech and language pathologist
  • Case manager
  • Neurologist
  • Neuropsychologist (psychologist)
  • Physiatrist
  • Psychiatrist
  • Social worker (counselor)
  • Vocational rehabilitation counselor

Traumatic Brain Injury VA Health Initiative
14
Comprehensive Assessment of Acquired Brain Injury
  • History
  • Accident related facts
  • Initial neurological presentation
  • Pre injury information
  • past medical history and surgical history
    substance abuse
  • developmental history
  • educational history.
  • Military and legal records
  • Vocational History
  • Psychological history
  • Life stressors
  • Family history
  • Post injury treatment interventions
  • Current functional status
  • Physical Examination
  • Neurological
  • Cranial nerves 1-12
  • Deep tendon reflexes and
    pathological
  • Sensory exam
  • Cerebellar exam
  • Motor exam
  • Mental status exam
  • Behavioral assessment
  • Emotional/psychological status
  • Musculoskeletal
  • Head
  • Face and temporomandibular joints
  • Extremities
  • Axial structures (neck, back,
    pelvis)

Traumatic Brain Injury VA Health Initiative
15
Chronic cognitive problems
  • Attention problems
  • New learning and memory problems
  • Executive control dysfunction
  • Others (orientation, communication, behavioral,
    bradyphrenia, etc)

Traumatic Brain Injury VA Health Initiative
16
Interplay of cognitive and emotional problems
  • Neurogenic symptoms
  • Anasognosia (lack of awareness of
    impairment)
  • Frustration, catastrophic reaction, reduce
    information
  • Lack of initiative, impaired emotional
    expressiveness (Aprosodias), lower
  • crying threshold, fatigue
  • Distractability, inabilityto deal with more
    than one task at a time, dependence on external
    controls.
  • Lability of emotional expressiveness (not
    the underlying feeling state)
  • Lack of initiative
  • Impaired planning
  • Aphasia, anomia, or confusion
  • Impulsivity, social disinhibition
  • Psychogenic/Psychiatry symptoms
  • Denial
  • Anger and irritability
  • Depression
  • Rigid compulsive/hypervigilant
  • Emotional lability
  • Social withdrawl
  • Sense of futurelessness
  • Thought disorder
  • Personality and conduct disorder

Traumatic Brain Injury VA Health Initiative
17
  • Acute PainNormal sensation triggered by the
    nervous system to alert you to possible injury.
  • Chronic PainPain persists, signals keep firing
    in the nervous system for weeks, months, even
    years

NINDS Chronic Pain information page
18
Pain
  • Tissue injury trigers an inflammatory cascade
    that will alter nociceptive function.
  • Plasticity and learning play a role in pain
  • Synaptic potentiation is facilitated by
    repetitive noxious stimulation and at the level
    of the brain,environmental influences alter the
    response to noxious stimulation.
  • The brain can generate pain in the absence of
    input from the peripheral nociceptors or the
    spinal cord. e.g. phantom limb pain
  • Therefore a Brain pattern generating mechanism or
    Neuromatrix has been proposed

Pain an overview, JD Loeser, R.Melzack . The
Lancet 1999 1607-1609
19
  • International association for the Study of
    Pain
  • Pain is an unpleasant sensory and emotional
    experience associated with actual or potential
    tissue damage or describe in terms of such
    damage

JD Loeser, R Melzack, The Lancet 1999 1607-1609
(Pain an overview)
20
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Components of Pain
  • Nociception detection of tissue damage by
    specialized transducers attached to A delta and C
    fibers. Aspirin can prevent inflammation and
    Local and regional anesthesia can prevent
    nociception.
  • Perception of Pain triggerd by noxious stimulus,
    It can be generated by lesion in the peripheral
    or central nervous system.e.g. diabetic
    neuropathy, spinal cord injury or stroke. Pain
    can occur without nociception. The intensity of
    chronic pain has no relation to the extent of
    tissue injury or other pathology.
  • Sufferingnegative response induce by pain and by
    fear, anxiety, stress, loss of loved objects and
    othr psychological states. CassellSuffering
    occurs when the physcial and psychological
    integrity of the person is threatened.
  • Pain Behaviors results from pain and suffering
    and the things the person do or does not do.
    Examplesouch, gramacing, limping, lying down ,
    recourse to health care, refusing to work, etc.

JD Loeser, R. Melzack, The Lancet 1999 1607-1609
(Pain an overview)
22
The neurobiology of pain, Besson JM The
Lancet,1999353 1610-1615
23
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Histamine, serotonin, bradykinin, prostaglandins,
ATP, H ,NGF, TNF alpha, endothelins, interleukins
25
Pain treatment options TCA, anticonvulsants, Na
channel blockers, NMDA receptor antagonists,
opioids
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Molecular Events of PainPeripheral
  • Transduction
  • TRPV1, TRPV2, TRPV3, TRPM8
  • ASCI, DRASIC
  • MDEG, TREK-1
  • BK1, BK2
  • P2K3
  • Peripheral sensitization
  • NGF, TrkA
  • TRPV1
  • Na, 1,8
  • PKA, PKC isoforms, CalMK IV
  • Erk1/2, p38, JNK
  • IL-1ß, cPLA2, COX2, EP1, EP3, EP4
  • TNFa
  • Membrane excitability of primary afferents
  • Nav 1.8, Nav 1.9
  • K channel
  • Synaptic transmission Presynaptic
  • VGCC

J.Scholz, CJ Woolf Can we conquer pain? , Nature
Neuroscience 2002 10621067
34
Molecular Events of PainCentral
  • Synaptic transmission Postsynaptic
  • AMPA/kainate-R, NMDA-R, mGlu-R
  • NK1
  • Nav 1.3
  • K channels
  • Central inhibition
  • GABA, GABAA-R, GABAB-R
  • Glycine-R
  • NE, 5-HT
  • Opioid receptors
  • CB1
  • Signal transduction
  • PKA, PC isoforms
  • ERK, p38, JNK
  • Gene expression
  • C-fos, c-jun, CREB
  • DREAM

J.Scholz, CJ Woolf Can we conquer pain? Nature
Neuroscience 2002 1062-1067
35
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The National Initiative on Pain Control, 2002
37
The National Initiative on Pain Control, 2002
38
The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
40
The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
42
The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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BRAIN IMAGING TECHNIQUES
  • PET
  • Requires relatively long pain stimulation periods
    (40 60s).
  • Different functional states (e.g., pain and rest)
    are always acquired in separate scans.
  • Maximum number of scans that can be acquired is
    limited by radioactivity dose restraints.
  • Usually requires multi-patient study designs.
  • Potential to map neurotransmitter systems and
    drug uptake in vivo and molecular imaging.
  • Provides a solution in cases where fMRI cannot be
    accomplished because of contraindications.
  • fMRI
  • Offers better temporal and spatial resolution
    than PET.
  • Pain stimuli do not need to be applied over along
    period.
  • The control state and the active pain condition
    are done in the same run.
  • Better suited than PET for studying cognitive
    effects on pain processing.
  • Unlimited amount of repetitions within a single
    patient, allowing single participant, and follow-
    up studies.
  • Offers less comfort to the patient (noise, body
    constrained in the magnet bone).
  • Requires expensive fMRI-compatible stimulation
    and monitoring equipment.
  • MEG
  • Allows mapping of the sequential activation of
    brain structures in pain processing.
  • Provides a direct measure of neuronal activity.
  • The most ecological technique with the highest
    comfort and least distress for participants.

Brain Imaging of clinical pain states..Kipers R,
Kehlet H. The Lancet Neurology 2006 51033-1044
47
Kupers R, Kehlet H The Lancet Neurology 2006
1033-1044
48
Temporal Spatial Resolution Resolution Advantag
es Disadvantages_________________________________
______________________________________
  • PET 49s 4 mm Measures activity
    and Radioactivity.
  • subcortical structures. Poor temporal
    resolution.
  • Stimulus-independent Invasive technique.
  • technique Limited amount of scans
  • Allows receptor binding possible.
  • studies
  • fMRI 100 ms 3s 2 mm Measures activity in Poor
    patient comfort.
  • cortical and structures. Requires non-magnetic
  • Excellent spatial equipment.
  • resolution. Stimulus-dependent
  • technique.
  • MEG Milliseconds 2 mm Excellent
    temporal Difficulties to measures
  • resolution. subcortical activity.
  • High patient comfort. Requires non-magnetic
  • Ecological method. equipment.
  • Stimulus-dependent technique.
  • __________________________________________________
    __________________________________

Kupers R, Kehlet H The Lancet Neurology
20061033-1044
49
Kupers R, Kehlet H, The Lancet Neurology
20061033-1044
50
METHODOLOGICAL DIFFICULTIES IN DESIGN OF
BRAIN-IMAGING STUDIES IN CHRONONIC PAIN
  • Difficulty in finding a homogeneous population of
    chronic-pain patients.
  • Difficulty in discerning pain-related from
    psychological-related effects.
  • Possible confound by differences in genetic
    constitution.
  • Difficulty in dissociation of deafferentiation-rel
    ated from pain-related changes in brain
    activation patterns.
  • Homologous contralateral area is not an unbiased
    site fro non-painful control stimulation.
  • Difficulty in switching pain on and off in a very
    precise and time-locked manner.
  • Effects of therapeutic interventions could be
    difficult to dissociate from pain-related
    effects.

Kupers R, Kehlet H.The Lancet Neurology
20061033-1044
51
B.R. Buchbinder, Division of Neuroradiology MGH,
Boston, MA
52
B.R.Buchbinder, Division of Neuroradiology MGH,
Boston, MA
53
Epidural Hematoma
Emergency Neuroradiology, M.Rothman et al.
e-medicine, Oct 29, 2003
54
Right subdural hematoma
Intraparenchymal bleeding
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
55
Left frontal contusion
Right linear contusion
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
56
Bullet
Emergency Neuroradiology, M Rothman, e-medicine
Oct 29, 2003
57
Metallic rod
Emergency Neuroradiology, M.Rothman, e-medicine
Oct 29, 2003
58
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