Traumatic Brain Injury and Pain

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Traumatic Brain Injury and Pain

• F.Antonio Luque, M.D. Ph.D.
• Neurology

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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

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TRAUMATIC BRAIN INJURY
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Military Fatalities By Time PeriodAs of 2/20/07
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US Non Mortal Casualties Including non-hostile
and medical evacuations As of 2/3/07
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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.

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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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• 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
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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
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• 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)
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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)
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The neurobiology of pain, Besson JM The
Lancet,1999353 1610-1615
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Histamine, serotonin, bradykinin, prostaglandins,
ATP, H ,NGF, TNF alpha, endothelins, interleukins
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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
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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
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The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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The National Initiative on Pain Control, 2002
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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
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Kupers R, Kehlet H The Lancet Neurology 2006
1033-1044
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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
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Kupers R, Kehlet H, The Lancet Neurology
20061033-1044
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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
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B.R. Buchbinder, Division of Neuroradiology MGH,
Boston, MA
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B.R.Buchbinder, Division of Neuroradiology MGH,
Boston, MA
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Epidural Hematoma
Emergency Neuroradiology, M.Rothman et al.
e-medicine, Oct 29, 2003
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Right subdural hematoma
Intraparenchymal bleeding
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
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Left frontal contusion
Right linear contusion
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
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Bullet
Emergency Neuroradiology, M Rothman, e-medicine
Oct 29, 2003
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Metallic rod
Emergency Neuroradiology, M.Rothman, e-medicine
Oct 29, 2003
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