Traumatic Brain Injury and Pain

Traumatic Brain Injury and Pain F.Antonio Luque, M.D. Ph.D. Neurology 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 TRAUMATIC BRAIN INJURY Military Fatalities: By Time Period As of 2/20/07 Period US UK Other* Total Avg Days 5 4 3 2 1 Total 998 715 579 718 140 3,150 34 13 25 27 33 132 21 1,053 18 27 58 0 746 631 803 173 2.43 2.35 2.92 1.89 4.02 434 318 216 424 43 124 3,406 2.37 1,435 US Non Mortal Casualties: Including nonhostile and medical evacuations As of 2/3/07 Non-Mortal Casualities Wounded – No Medical Air Transport Required Wounded – Medical Air Transport Required Non-Hostile Injuries – Medical Air Transport Required Disease – Medical Air Transport Required TOTAL – WOUNDED TOTAL – MEDICAL AIR TRANSPORTED Army 10,120 5,009 5,439 16,111 15,129 26,559 Navy 385 137 223 544 522 904 Marines 5,698 1,804 895 1,209 7,502 3,908 Air Force 209 55 278 840 264 1,173 Total 16,412 7,005 6,835 18,704 23,417 32,544 Traumatic Brain Injury Traumatic brain injury symptoms Inability to find words Inability to perform tasks Confabulating (putting unrelated bits of conversation into conversation gaps) Impulsivity Agitation Poor judgment and poor insight Sexual inappropriateness, including a lack of sexual inhibitions For more information, call (800) 877-VETS, or visit www.va.gov. Frequency of PCS Symptoms following a MTBI • • • • • • • • • • • Poor concentration Irritability Tired a lot more Depression Memory problems Headaches Anxiety Trouble thinking Dizziness Blurry or double vision Sensitivity to bright light 71% 66% 64% 63% 59% 59% 58% 57% 52% 45% 40% Traumatic Brain Injury, VA Health Initiative 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 Severity Grades of TBI • Mild (Grade 1 ): altered or LOC <30 min with normal CT or MRI, GCS 13-15, PTA < 24 hours. • Moderate (Grade 2): LOC < 6 hours with abnormal CT and/or MRI, GCS 9-12, PTA < 7 days. • Severe (Grade 3 & 4): LOC > 6 hours with abnormal CT and/or MRI, GCS < 9, PTA > 7 days. Traumatic Brain Injury VA Health Initiative 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 Frequency of PCS Symptoms following a MTBI • • • • • • • • • • • Poor concentration Irritability Tired a lot more Depression Memory problems Headaches Anxiety Trouble thinking Dizziness Blurry or double vision Sensitivity to bright light 71% 66% 64% 63% 59% 59% 58% 57% 52% 45% 40% Traumatic Brain Injury, VA Health Initiative 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 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 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 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 Interplay of cognitive and emotional problems Psychogenic/Psychiatry symptoms Denial Anger and irritability Depression Rigid compulsive/hypervigilant Emotional lability Social withdrawl Sense of futurelessness Thought disorder Personality and conduct disorder 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 Traumatic Brain Injury VA Health Initiative • Acute Pain:”Normal sensation triggered by the nervous system to alert you to possible injury.” • Chronic Pain:”Pain persists, signals keep firing in the nervous system for weeks, months, even years” NINDS Chronic Pain information page 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 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) 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. • Suffering:negative response induce by pain and by fear, anxiety, stress, loss of loved objects and othr psychological states. Cassell:”Suffering 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. Examples:”ouch”, gramacing, limping, lying down , recourse to health care, refusing to work, etc. JD Loeser, R. Melzack, The Lancet 1999: 1607-1609 (Pain: an overview) The neurobiology of pain, Besson JM The Lancet,1999:353: 1610-1615 Histamine, serotonin, bradykinin, prostaglandins, ATP, H+ ,NGF, TNF alpha, endothelins, interleukins Pain treatment options: TCA, anticonvulsants, Na+ channel blockers, NMDA receptor antagonists, opioids Molecular Events of Pain Peripheral 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-1β, cPLA2, COX2, EP1, EP3, EP4 • TNFα Membrane excitability of primary afferents • Nav 1.8, Nav 1.9 • K+ channel Synaptic transmission Presynaptic • VGCC • Adenosine-R • (mGlu-R) J.Scholz, CJ Woolf: Can we conquer pain? , Nature Neuroscience 2002: 10621067 Molecular Events of Pain Central 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 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 The National Initiative on Pain Control, 2002 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 followup 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. • Allows conclusions from single trial and single participant studies (great clinical potential). Brain Imaging of clinical pain states..Kipers R, Kehlet H. The Lancet Neurology 2006: 5:1033-1044 Kupers R, Kehlet H The Lancet Neurology 2006: 1033-1044 Temporal Spatial Resolution Resolution Advantages Disadvantages _______________________________________________________________________ PET >49’s >4 mm Measures activity and subcortical structures. Stimulus-independent technique Allows receptor binding studies Measures activity in cortical and structures. Excellent spatial resolution. Radioactivity. Poor temporal resolution. Invasive technique. Limited amount of scans possible. fMRI 100 ms – 3’s >2 mm Poor patient comfort. Requires non-magnetic equipment. Stimulus-dependent technique. Difficulties to measures subcortical activity. Requires non-magnetic equipment. Stimulus-dependent technique. ____________________________________________________________________________________ Characteristics of different brain imaging techniques used in the study of pain. MEG Milliseconds >2 mm Excellent temporal resolution. High patient comfort. Ecological method. Kupers R, Kehlet H The Lancet Neurology 2006:1033-1044 Kupers R, Kehlet H, The Lancet Neurology 2006:1033-1044 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-related from pain-related changes in brain activation patterns. • Homologous contralateral area is not an unbiased site fro nonpainful control stimulation. • Difficulty in switching pain on and off in a very precise and timelocked manner. • Effects of therapeutic interventions could be difficult to dissociate from pain-related effects. Kupers R, Kehlet H.The Lancet Neurology 2006:1033-1044 B.R. Buchbinder, Division of Neuroradiology MGH, Boston, MA B.R.Buchbinder, Division of Neuroradiology MGH, Boston, MA Epidural Hematoma Emergency Neuroradiology, M.Rothman et al. e-medicine, Oct 29, 2003 Intraparenchymal bleeding Right subdural hematoma Head Injury, Olson DA et al. e-Medicine Oct 2, 2006 Left frontal contusion Right linear contusion Head Injury, Olson DA et al. e-Medicine Oct 2, 2006 Bullet Emergency Neuroradiology, M Rothman, e-medicine Oct 29, 2003 Metallic rod Emergency Neuroradiology, M.Rothman, e-medicine Oct 29, 2003