Title: Traumatic Brain Injury and Pain
1Traumatic Brain Injury and Pain
- F.Antonio Luque, M.D. Ph.D.
- Neurology
2Traumatic 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
3TRAUMATIC BRAIN INJURY
4Military Fatalities By Time PeriodAs of 2/20/07
5US Non Mortal Casualties Including non-hostile
and medical evacuations As of 2/3/07
6Traumatic 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.
7Frequency 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
8Causes 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
9Severity 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
10Functional 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
11Frequency 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
12Specific 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
13Referrals ( 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
14Comprehensive 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
15Chronic cognitive problems
- Attention problems
- New learning and memory problems
- Executive control dysfunction
- Others (orientation, communication, behavioral,
bradyphrenia, etc)
Traumatic Brain Injury VA Health Initiative
16Interplay 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
18Pain
- 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(No Transcript)
21Components 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)
22The neurobiology of pain, Besson JM The
Lancet,1999353 1610-1615
23(No Transcript)
24Histamine, serotonin, bradykinin, prostaglandins,
ATP, H ,NGF, TNF alpha, endothelins, interleukins
25Pain treatment options TCA, anticonvulsants, Na
channel blockers, NMDA receptor antagonists,
opioids
26(No Transcript)
27(No Transcript)
28(No Transcript)
29(No Transcript)
30(No Transcript)
31(No Transcript)
32(No Transcript)
33Molecular 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
34Molecular 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(No Transcript)
36The National Initiative on Pain Control, 2002
37The National Initiative on Pain Control, 2002
38The National Initiative on Pain Control, 2002
39The National Initiative on Pain Control, 2002
40The National Initiative on Pain Control, 2002
41The National Initiative on Pain Control, 2002
42The National Initiative on Pain Control, 2002
43(No Transcript)
44The National Initiative on Pain Control, 2002
45(No Transcript)
46BRAIN 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
47Kupers 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
49Kupers R, Kehlet H, The Lancet Neurology
20061033-1044
50METHODOLOGICAL 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
51B.R. Buchbinder, Division of Neuroradiology MGH,
Boston, MA
52B.R.Buchbinder, Division of Neuroradiology MGH,
Boston, MA
53Epidural Hematoma
Emergency Neuroradiology, M.Rothman et al.
e-medicine, Oct 29, 2003
54Right subdural hematoma
Intraparenchymal bleeding
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
55Left frontal contusion
Right linear contusion
Head Injury, Olson DA et al. e-Medicine Oct 2,
2006
56Bullet
Emergency Neuroradiology, M Rothman, e-medicine
Oct 29, 2003
57Metallic rod
Emergency Neuroradiology, M.Rothman, e-medicine
Oct 29, 2003
58(No Transcript)