Central Sensitization           © Matthew B. Smith, 2010             Matthew B. Smith, M.D.         Faculty, NYU School of...
Central Sensitization:       Outline• General• Plasticity• Pain Matrix• Clinical and Secondary• Complexity Theory• Psychol...
Definitions: Acute Pain,    Chronic Pain• Time • 3-6 months• Mechanism • Central Sensitization
Pain Afferents
Pain Afferents•   A-delta fibers    •   First pain    •   Myelinated    •   Large    •   Pressure, heat
Pain Afferents•   A-delta fibers          •   C fibers    •   First pain             •   Second pain    •   Myelinated      ...
Pain Afferents•   A-delta fibers          •   C fibers                                                  •   Second Order    ...
Peripheral SensitizationGiordano. The neurobiology of nociceptive and anti-nociceptive systems. Pain physician (2005) vol....
Central Sensitization:  Neuronal Plasticity• Synaptic plasticity: Hebbian• Non-Hebbian Plasticity
Synaptic Plasticity:                    Hebbian Theory•Hebb DO. 1949. The Organization of Behavior; A Neuropsychological T...
Synaptic Plasticity:                    Hebbian Theory  • “When an axon of cell A is near enough to excite a cell B and  r...
•   Strong Afferent    Stimulation
Synaptic Plasticity: LTP•   Strong Afferent    Stimulation
Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human)     5/6/08 12:49 PM       •      Stron...
Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human)              5/6/08 12:49 PM       •  ...
Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human)              5/6/08 12:49 PM       •  ...
LTP: Temporal Summation   (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
LTP: Temporal Summation   (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
LTP: Temporal Summation   (Kindling, Windup)       1       2       3       4 (Also, spatial summation -- from different pr...
LTP: Temporal Summation   (Kindling, Windup)       1       2       3       4       5      6 (Also, spatial summation -- fr...
LTP: Post-Tetanic  Facilitation
LTP: Post-Tetanic  Facilitation
LTP: Post-Tetanic  Facilitation
LTP: Post-Tetanic  Facilitation
LTP: Post-Tetanic  Facilitation
LTP: Spike timing dependent plasticity, concidence                           .05 msec
260          LTP: Regional Variation                            A Synaptic Model for Pain: Long-Term Potentiation in the A...
Synaptic Plasticity: Synaptic States Montgomery et al. Discrete synaptic states define a major mechanism of synapse        ...
Non-Hebbian Neuronal     Plasticity• Long-term Depression• Neuroanatomic spreading• Ephaptic Crosstalk
Central Sensitization Mechanisms: LTD    KEGG PATHWAY: Long-term depression - Homo sapiens (human)            5/6/08 12:50...
Neuroanatomic Spreading
Neuroanatomic Spreading
Neuroanatomic Spreading
Neuroanatomic Spreading
Ephaptic Crosstalk            ephapse            A place where two or more            nerve cell processes (axons,        ...
Changes with Neuronal Plasticity in Chronic• Morphologic• Neurochemical• Immunologic• Neuronal loss• Sensory Processing
Morphologic Changes in                   Neuronal Plasticity               • Axonal sprouting and pruning               • ...
Neurochemical Changes in•   Pain afferents                                                 •     Central    •   Glutamate,...
Neurochemical Changes:         Dopamine                  Increased tonic dopamine level                                   ...
Central Sensitization, Immunological : Microglia, Astrocytes    Deleo et al. The tetrapartite synapse: Path to CNS sensiti...
Central Sensitization,        Neuronal Loss: Apoptosis•      Loss of spinal cord       inhibitory interneurons•      Loss ...
Sensory Processing:        Deafferentation,          AllodyniaWoolf et al. The pathophysiology of chronic pain--increased ...
Sensory Processing:        Deafferentation,          Allodynia                          Primary Pain                      ...
Sensory Processing:        Deafferentation,          Allodynia                          Primary Pain                      ...
Sensory Processing:        Deafferentation,          Allodynia                          Primary Pain                      ...
Sensory Processing:        Deafferentation,          Allodynia                             Touch                          ...
Sensory Processing:        Deafferentation,          Allodynia                             Touch                          ...
Sensory Processing:        Deafferentation,          Allodynia                          Primary Pain                      ...
Sensory Processing:        Deafferentation,          Allodynia                          Primary Pain                      ...
Melzack: Gate Control                                  Theory                                          -     P----        ...
Central Sensitization:       Spinothalamic Tracts,        Pain Amplification•   Descending Modulatory Pathways
Central Sensitization:       Spinothalamic Tracts,        Pain Amplification•   Descending Modulatory Pathways             ...
Central Sensitization:       Spinothalamic Tracts,        Pain Amplification•   Descending Modulatory Pathways             ...
Central Sensitization:       Spinothalamic Tracts,        Pain Amplification•   Descending Modulatory Pathways             ...
Central Sensitization: Spinothalamic          Tracts, Pain Amplification                                                 Th...
Central Sensitization: Spinothalamic          Tracts, Pain Amplification•    Hypothalamus:               •   Amygdala: Fear...
Central Sensitization: Thalamus, Pain                    Amplification Frontal Cortex    Somatosensory Cortex   Anterior Ci...
Central Sensitization: Thalamus, Pain                    Amplification  •     Frontal Cortex: cognitive, executive         ...
Pain MatrixJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
Pain Matrix    Prefrontal                                                          Somatosensory                          ...
Pain Matrix    Prefrontal                                                          Somatosensory                          ...
Pain Matrix    Prefrontal                                                          Somatosensory                          ...
Pain Matrix    Prefrontal                                                          Somatosensory                          ...
Central Sensitization: Brain Illness               Grachev et al. Abnormal brain chemistry in chronic back pain: an in viv...
Central Sensitization: Brain Illness   •      Cortical Reorganization               Grachev et al. Abnormal brain chemistr...
Central Sensitization: Brain Illness   •      Cortical Reorganization   •      Pain matrix               Grachev et al. Ab...
Central Sensitization: Brain Illness   •      Cortical Reorganization   •      Pain matrix         •      No single pain g...
Central Sensitization: Brain Illness   •      Cortical Reorganization   •      Pain matrix         •      No single pain g...
Central Sensitization: Brain Illness   •      Cortical Reorganization   •      Pain matrix                                ...
Central Sensitization: Brain Illness   •      Cortical Reorganization   •      Pain matrix                                ...
Central Sensitization• Malignant process of up-regulation, pain begetting  more pain, becoming autonomous• Counterintuitiv...
Central Sensitization: Additional and          Clinical Aspects    •   Secondary hyperalgesia    •   Geographic Spread    ...
Central Sensitization:  Secondary Hyperalgesia• Reduced threshold• Hyperpathia• Paresthesia• Numbness
Central Sensitization: Geographic spread                                              •    Centrifugal spread             ...
Central Sensitization: Modality Effects •    Allodynia •    Variable quality •    Cross-modality sensitization     •   Pho...
Central Sensitization:  Temporal Effects• Persistence, longer after-sensations• Spontaneous, unpredictable exacerbations• ...
Central Sensitization:      Loss of DNIC•   “Diffuse Noxious Inhibitory Controls”•   Usually inhibit additional pain•   Fa...
Hormonal Effects:        Stress Response   •       Hypothalamus - Pituitary -           Adrenal   •       Cortisol        ...
Central Sensitization: Sympathetic System• Dysautonomia   • Persistent hyperactivation   • Paradoxical hyporeactivity to s...
Central Sensitization:         Autonomic Effects•   Hyperhydrosis•   Arousal/Non-arousal             •   Local Changes    ...
Central Sensitization: Movement Effects    • Difficulty in initiation, maintenance, and precision of        small movements...
Central Sensitization:   Systemic Effects• Sleep disturbance• Fatigue• Circadian Rhythm disruption• Development of Additio...
Central Sensitization: Psychological Effects • Augmented intrinsic effects     • Cognitive/executive     • Fear     • Ange...
Central Sensitization•   Pain comes to dominate subjective experience, activity•   Pain as pre-eminent psychic funnel, org...
“Complexity,” Chaos, Dynamic Systems Theory:                 Sustaining      Martinez-Lavin et al. Hypothesis: the chaos a...
“Complexity,” Chaos, Dynamical System             Theory: Sustaining•   Nonlinearity•   Self-organization•   “Emergent” bi...
“Complexity,” Chaos, Dynamical System             Theory: Sustaining•   Nonlinearity•   Self-organization•   “Emergent” bi...
“Complexity,” Chaos, Dynamical System             Theory: Sustaining•   Nonlinearity•   Self-organization•   “Emergent” bi...
“Complexity,” Chaos, Dynamical System             Theory: Sustaining•   Nonlinearity•   Self-organization•   “Emergent” bi...
“Complexity,” Chaos, Dynamical System             Theory: Sustaining•   Nonlinearity•   Self-organization•   “Emergent” bi...
Central Sensitization:     Additional• Self Image• Trauma
Somatosensory Cortex            •    Homunculus                                                     •    Routine persisten...
Somatosensory Cortex            •    Homunculus                                                     •    Routine persisten...
Somatosensory Cortex            •    Homunculus                                                     •    Routine persisten...
Somatosensory Cortex            •    Homunculus                                                     •    Routine persisten...
Effects of Centralization: Change in self         Peyron et al. Functional imaging of brain responses to pain. A review an...
Effects of Centralization: Change in self•   Change in body schema related to            Peyron et al. Functional imaging ...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Effects of Centralization: Change in self•   Change in body schema related to    •   total amount of body surface stimulat...
Self, Identity                                                          Values                                     Conscie...
Change in Self: Modified       “Broken Selves”          Robert S. Beal
Psychological TraumaGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during h...
Psychological Trauma                                       • Powerful Stimulus                                         • S...
Psychological Trauma                                       • Powerful Stimulus                                         • S...
Psychological Trauma                                       • Powerful Stimulus                                         • S...
Psychological Trauma                                       • Powerful Stimulus                                         • S...
Chronic Pain as Continued  Psychological Trauma •   Inescapable     Stimulus •   Chronicity
Chronic Pain as Continued          Psychological Trauma•   Psychological load    •   augmented aversive effects, pain     ...
Chronic Pain as Continued  Psychological Trauma
Chronic Pain as Continued  Psychological Trauma  • Shame
Chronic Pain as Continued  Psychological Trauma  • Shame    • Control
Chronic Pain as Continued  Psychological Trauma  • Shame    • Control  • Narcissistic mortification
Chronic Pain as Continued  Psychological Trauma  • Shame    • Control  • Narcissistic mortification  • Guilt, self-blame
Chronic Pain as Continued Psychological Trauma
Chronic Pain as Continued Psychological Trauma     • Regression
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations              •   Dep...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Chronic Pain as Continued Psychological Trauma     • Regression        •   Primitive Object Relations             •   Depe...
Title:   Echoes Of Sadness                            Media:     chalk on paper    Chronic Pain as Continued Psychological...
%&(&)*$+",&-&.#&/"01+"1223    Chronic Pain as Continued Psychological Trauma                         I&?*8&J"G3C)$B*H/$)"+...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
+*81>?"*@>*A>)#"*B"                                                                                                       ...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain as Continued Psychological Trauma•   Damaging to “Self”    •   Loss of “Self”    •   Damaged “Self”    •   Br...
Chronic Pain: “Self” Conflict II•   Inability to    assimilate pain•   Pain as foreign    body, parasite•   Unresolved
Chronic Pain: “Self” Conflict II•   Inability to    assimilate pain•   Pain as foreign    body, parasite•   Unresolved
Chronic Pain: “Self” Conflict II•   Inability to    assimilate pain•   Pain as foreign    body, parasite•   Unresolved
Central Sensitization: Summary   of Psychological Effects   •   Amplification of aversive features   •   Pain as central fo...
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Central Sensitization In Chronic Pain

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  • Pain always has a psychology. Threrfore, Chronic pain is a pathological conditions that has associated psychopathology. \nChronic pain isv complex, and the associated psychopathology is also v complex, and often dramatic. Treating the pain, dealing w the pts calls for an underrstanding of the psycho path.\nChronic pain always has associated psychopathology that contributes to the subjective suffering and dbi, and becomes difficult to disentagle fm the physical. \nChr pain is different fm oth conditions, which often, b don’t intrinsically involve psychopathology. \nNot arguing that all pts need to see psychiatrists\n
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  • Neurotoxicity of cortisol\nLongterm potentiation, sensitization.involvement of further CNS structures, at the level of both SPINAL CORD and brain.\nLoss of compensatory systems. \nDevelopment of a complex pain matrix. \nAmplification of pain experience, with reduction of pain threshold and tolerance. \nReorganization at multiple levels including the somatosensory cortex. Greater prominence of the hurting body part, and greater intensity. \n\n\n\n
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  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  • Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
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  • Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  • Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  • Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  • Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  • In acute pain, there is a useful bottom line coping mechanism: the belief that the pain will pass, be treated, will go away. \nBut, in chronic pain, it will be there later today, tomorrow, next week, next month, next year, 2 years hence, 5 years, 10 years, rest of life. \n
  • No innate capacity to say that the alarm of pain is not an alarm, is actually meaningless and we can carry on. \nContinued experience of threat, danger, which worsens, when chronic, and not only cna’t be ignored, but actually intrudes more prominently across our psychological barrier. Breaks the stimulus barrier. Internally, eats away at the self, the soul. \nBreach of the stimulus barrier\nLack of control, helplessness\nAs it becomes a part of self, there is a subjective imperative to control, with a reaction to the inability to control. \nSensation, fear, anger are experienced as out of control, when they should be in control, ie, as incontinence, with shame. E.g., the patient who says he/she hears from his doc that the pain shouldn’t really be there, be that bad, so the patient thinks it must be his doing, and is ashamed. \n“Mortification” is shame on steroids, and appropriate, since this is daily and global. \n“Narcissistic mortification” refers to existential dismay at our powerlessness in the face of overwhelming circumstances; having our faces rubbed in our powerlessness. My own example: what I felt regarding 9/11. Also refers to how the mortification itself is now incorporated into the self. \n\n\n
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  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
  • Regression -- relative permanence of the emotions and behaviors associated with pain\nObject relas:\nLoss of soothing\nall good/bad, e.g., self, important relationships, in cluding family and doc, world\nmostly all bad\ncan take on meaning of their indifference, their persecution\ngood -- all good on good days, or, good as hope for the future, fantasy. \nrelationships\nLoss of self, in addition to other losses\nIdiosyncratic meaning -- pain has meaning, ie, punishment, victim status, etc. \n\n
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  • Central Sensitization In Chronic Pain

    1. 1. Central Sensitization © Matthew B. Smith, 2010 Matthew B. Smith, M.D. Faculty, NYU School of Medicine General Adult psychiatryLiaison Psychiatrist, NYU Pain Management Team Liaison Psychiatrist, NYU Palliative Care Team
    2. 2. Central Sensitization: Outline• General• Plasticity• Pain Matrix• Clinical and Secondary• Complexity Theory• Psychological Effects
    3. 3. Definitions: Acute Pain, Chronic Pain• Time • 3-6 months• Mechanism • Central Sensitization
    4. 4. Pain Afferents
    5. 5. Pain Afferents• A-delta fibers • First pain • Myelinated • Large • Pressure, heat
    6. 6. Pain Afferents• A-delta fibers • C fibers • First pain • Second pain • Myelinated • Unmyelinated • Large • Small • Pressure, heat • Polymodal
    7. 7. Pain Afferents• A-delta fibers • C fibers • Second Order Neurons • First pain • Second pain • Myelinated • Unmyelinated • WDR (Wide Dynamic Range) • Large • Small • HT (High • Pressure, heat • Polymodal Threshold) • LT (Low Threshold)
    8. 8. Peripheral SensitizationGiordano. The neurobiology of nociceptive and anti-nociceptive systems. Pain physician (2005) vol. 8 (3) pp. 277-90
    9. 9. Central Sensitization: Neuronal Plasticity• Synaptic plasticity: Hebbian• Non-Hebbian Plasticity
    10. 10. Synaptic Plasticity: Hebbian Theory•Hebb DO. 1949. The Organization of Behavior; A Neuropsychological Theory. New York: Wiley. xix, 335 pp.
    11. 11. Synaptic Plasticity: Hebbian Theory • “When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.” •“Cells that fire together, wire together.”•Hebb DO. 1949. The Organization of Behavior; A Neuropsychological Theory. New York: Wiley. xix, 335 pp.
    12. 12. • Strong Afferent Stimulation
    13. 13. Synaptic Plasticity: LTP• Strong Afferent Stimulation
    14. 14. Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human) 5/6/08 12:49 PM • Strong Afferent Long-term potentiation - Homo sapiens (human) Stimulation [ Pathway menu | Reference list ] Homo sapiens (human) Go Current selection
    15. 15. Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human) 5/6/08 12:49 PM • Strong Afferent Long-term potentiation - Homo sapiens (human) • Synapse Growth Stimulation [ Pathway menu | Reference list ] Homo sapiens (human) Go Current selection Proteins
    16. 16. Synaptic Plasticity: LTPKEGG PATHWAY: Long-term potentiation - Homo sapiens (human) 5/6/08 12:49 PM • Strong Afferent Long-term potentiation - Homo sapiens (human) • Synapse Growth Stimulation [ Pathway menu | Reference list ] Homo sapiens (human) Go Current selection Proteins
    17. 17. LTP: Temporal Summation (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
    18. 18. LTP: Temporal Summation (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
    19. 19. LTP: Temporal Summation (Kindling, Windup) 1 2 3 4 (Also, spatial summation -- from different presynaptic neurons)
    20. 20. LTP: Temporal Summation (Kindling, Windup) 1 2 3 4 5 6 (Also, spatial summation -- from different presynaptic neurons)
    21. 21. LTP: Post-Tetanic Facilitation
    22. 22. LTP: Post-Tetanic Facilitation
    23. 23. LTP: Post-Tetanic Facilitation
    24. 24. LTP: Post-Tetanic Facilitation
    25. 25. LTP: Post-Tetanic Facilitation
    26. 26. LTP: Spike timing dependent plasticity, concidence .05 msec
    27. 27. 260 LTP: Regional Variation A Synaptic Model for Pain: Long-Term Potentiation in the Anterior Cingulate CortexGTable 1. Long-term potentiation (LTP) recorded from sensory- Arelated central synapses. Induction protocol LTPPrefrontal frontal cortex TBS + (PFC) Paired training +Anterior cingulate cortex Strong tetanic stimulation − (ACC) TBS + Paired training + Spike-timing protocol +Insular cortex TBS +Somatosensory cortex TBS +Hippocampus Strong tetanic stimulation + B TBS + Paired training + Spike-timing protocol +amygdala Strong tetanic stimulation −/+ TBS + Paired training + Spike-timing protocol +Thalamus ND NDPeriaqueductal gray (PAG) ND NDRostroventral medulla ND ND (RVM)Spinal dorsal horn Strong tetanic stimulation −/+ Zhuo. A synaptic model for pain: long-term TBS + potentiation in the anterior cingulate cortex. Mol Paired training + Cells (2007) vol. 23 (3) pp. 259-71 Fig. 1. Diagram of the mouse anterior cingulate cortex (ACC). A. Spike-timing protocol ND An unilateral coronal section the mouse brain containing the ACC+, significant potentiation; −, no potentiation; +/−, potentiation only and adjacent brain areas. cg1, cingulate cortex, area 1; cg2, cingu-
    28. 28. Synaptic Plasticity: Synaptic States Montgomery et al. Discrete synaptic states define a major mechanism of synapse plasticity. Trends Neurosci (2004) vol. 27 (12) pp. 744-50
    29. 29. Non-Hebbian Neuronal Plasticity• Long-term Depression• Neuroanatomic spreading• Ephaptic Crosstalk
    30. 30. Central Sensitization Mechanisms: LTD KEGG PATHWAY: Long-term depression - Homo sapiens (human) 5/6/08 12:50 PM Long-term depression - Homo sapiens (human) [ Pathway menu | Reference list ] Homo sapiens (human) Go Current selection
    31. 31. Neuroanatomic Spreading
    32. 32. Neuroanatomic Spreading
    33. 33. Neuroanatomic Spreading
    34. 34. Neuroanatomic Spreading
    35. 35. Ephaptic Crosstalk ephapse A place where two or more nerve cell processes (axons, dendrites) touch without forming a typical synaptic contact
    36. 36. Changes with Neuronal Plasticity in Chronic• Morphologic• Neurochemical• Immunologic• Neuronal loss• Sensory Processing
    37. 37. Morphologic Changes in Neuronal Plasticity • Axonal sprouting and pruning • Dendritic sprouting and pruningGoldin et al. Functional plasticity triggers formation and pruning of dendritic spines in cultured hippocampal networks. J Neurosci (2001) vol. 21 (1) pp. 186-93Engert et al. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature (1999) vol. 399 (6731) pp. 66-70 Bock et al. Blockade of N-methyl-D-aspartate receptor activation suppresses learning-induced synaptic elimination. Proc Natl Acad Sci USA (1999) vol. 96 (5) pp. 2485-90
    38. 38. Neurochemical Changes in• Pain afferents • Central • Glutamate, Substance P, • NMDA activation Calcium • Reduced endogenous opioids • Increased CCK- mediated opioid • Reduced serotonin antagonism • 5HT2A Up regulation • Norepinephrine changes • Dopamine changes Smith. Serotonin mechanisms in pain and functional syndromes: management implications in comorbid fibromyalgia, headache, and irritable bowl syndrome-case study and discussion. J Pain Palliat Care Pharmacother (2004) vol. 18 (4) pp. 31-45
    39. 39. Neurochemical Changes: Dopamine Increased tonic dopamine level Pain and stress syndromes Reduced phasic dopamine signal• Anhedonia • Lack of Motivation Siri Leknes et al. A common neurobiology for pain and pleasure. Nat Rev Neurosci (2008) vol. 9 (4) pp. 314
    40. 40. Central Sensitization, Immunological : Microglia, Astrocytes Deleo et al. The tetrapartite synapse: Path to CNS sensitization and chronic pain. Pain (2006) vol. 122 (1-2) pp. 17-21 Scholz et al. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci (2007) vol. 10 (11) pp. 1361-8 Gabbard. Astroglia: Not Just Glue. Journal of Neuropsychiatry and Clinical Neurosciences (2008)s
    41. 41. Central Sensitization, Neuronal Loss: Apoptosis• Loss of spinal cord inhibitory interneurons• Loss of gray matter• Reduction in brain mass Whiteside et al. Cell death in the superficial dorsal horn in a model of neuropathic pain. Journal of Neuroscience Research (2001) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004) Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    42. 42. Sensory Processing: Deafferentation, AllodyniaWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    43. 43. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    44. 44. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    45. 45. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    46. 46. Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    47. 47. Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    48. 48. Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    49. 49. Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn AfferentWoolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
    50. 50. Melzack: Gate Control Theory - P---- LUJi;lllVI;L WILIIUMb- ,iort fibers and by the toagrof Lissauers tract (37, 38), but project outside the substantia sa. Recent evidence (39) sug-hat the substantia gelatinosa acts ate control system that modu- e synaptic transmission of nerve s from peripheral fibers to cen- s.re 4 shows the factors involved transmission of impulses from ral nerve to T cells in the cord. studies (39-41) have shownlleys of nerve impulses in large are extremely effective initially vating the T cells but that theirffect is reduced by a negativeck mechanism. In contrast, vol- Fig. 4. Schematic diagram of the gate control theory of pain mechanisms: L, the small fibers activate a positive large-diameter fibers; S, the small-diameter fibers. The fibers project to the substantiack mechanism which exaggerates gelatinosa (SG) and first central transmission (T) cells. The inhibitory effect exerted by SG on the afferent fiber terminals is increased by activity in L fibers and decreased byect of arriving impulses. Experi- activity in S fibers. The central control trigger is represented by a line running from (37, 39, 41) have shown that rg on July 20, 2008 the large-fiber system to the central control mechanisms; these mechanisms, in turn, eedback effects are mediated by project back to the gate control system. The T cells project to the entry cells of the the substantia gelatinosa. Ac- action system. +, Excitation; -, inhibition (see text). in these cells modulates theane potential of the afferenterminals and thereby determines If the stimulus intensity is increased, that pain results after prolonged moni-citatory effect of arriving im- more receptor-fiber units are recruited toring of the afferent input by central
    51. 51. Central Sensitization: Spinothalamic Tracts, Pain Amplification• Descending Modulatory Pathways
    52. 52. Central Sensitization: Spinothalamic Tracts, Pain Amplification• Descending Modulatory Pathways Thalamus Dorsal Horn
    53. 53. Central Sensitization: Spinothalamic Tracts, Pain Amplification• Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
    54. 54. Central Sensitization: Spinothalamic Tracts, Pain Amplification• Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
    55. 55. Central Sensitization: Spinothalamic Tracts, Pain Amplification ThalamusHypothalamus Septum VTA Amygdala PAGSympathetic Magnocellular Nucleus Dorsal Horn
    56. 56. Central Sensitization: Spinothalamic Tracts, Pain Amplification• Hypothalamus: • Amygdala: Fear, • PAG: Motivation Stress, Sympathetic Motivation• VTA: Motivation, • Septum: Emotion, Movement Motivation ThalamusHypothalamus Septum VTA Amygdala PAGSympathetic Magnocellular Nucleus Dorsal Horn
    57. 57. Central Sensitization: Thalamus, Pain Amplification Frontal Cortex Somatosensory Cortex Anterior Cingulate Cortex Insula Amygdala Striatum Thalamus Staud et al. Brain activity related to temporal summation of C-fiber evoked pain. Pain (2007)Burgmer et al. Altered brain activity during pain processing in fibromyalgia. Neuroimage (2009) vol. 44 (2) pp 502-8
    58. 58. Central Sensitization: Thalamus, Pain Amplification • Frontal Cortex: cognitive, executive • ACC, Insula, Limbic System: anxiety, functions depression • SSC: Bodily experience • Striatum: movement, initiation Frontal Cortex Somatosensory Cortex Anterior Cingulate Cortex Insula Amygdala Striatum Thalamus Staud et al. Brain activity related to temporal summation of C-fiber evoked pain. Pain (2007)Burgmer et al. Altered brain activity during pain processing in fibromyalgia. Neuroimage (2009) vol. 44 (2) pp 502-8
    59. 59. Pain MatrixJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
    60. 60. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal CordJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
    61. 61. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal CordJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
    62. 62. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal CordJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
    63. 63. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal CordJones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
    64. 64. Central Sensitization: Brain Illness Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    65. 65. Central Sensitization: Brain Illness • Cortical Reorganization Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    66. 66. Central Sensitization: Brain Illness • Cortical Reorganization • Pain matrix Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    67. 67. Central Sensitization: Brain Illness • Cortical Reorganization • Pain matrix • No single pain generator Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    68. 68. Central Sensitization: Brain Illness • Cortical Reorganization • Pain matrix • No single pain generator • Multiple mutually reinforcing resonances Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    69. 69. Central Sensitization: Brain Illness • Cortical Reorganization • Pain matrix • Thalamocortical dysrhythmia (Llinas) • No single pain generator • Multiple mutually reinforcing resonances Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    70. 70. Central Sensitization: Brain Illness • Cortical Reorganization • Pain matrix • Thalamocortical dysrhythmia (Llinas) • No single pain generator • Tends to persist even with • Multiple mutually reduced peripheral input reinforcing resonances Grachev et al. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy …. Pain (2000) Apkarian et al. Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density. Journal of Neuroscience (2004)Baliki et al. Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. Journal of Neuroscience (2008) vol. 28 (6) pp. 1398 Llinás et al. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA (1999) vol. 96 (26) pp. 15222-7 Kuchinad et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?. J Neurosci (2007) vol. 27 (15) pp. 4004-7 Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain (2006) vol. 125 (1-2) pp. 89-97
    71. 71. Central Sensitization• Malignant process of up-regulation, pain begetting more pain, becoming autonomous• Counterintuitive • No systemic homeostatic return to baseline • Patient does not learn to adjust to pain
    72. 72. Central Sensitization: Additional and Clinical Aspects • Secondary hyperalgesia • Geographic Spread • Modality effects • Temporal effects • Stress • Autonomic effects • Movement effects • Systemic effects • Psychological effects
    73. 73. Central Sensitization: Secondary Hyperalgesia• Reduced threshold• Hyperpathia• Paresthesia• Numbness
    74. 74. Central Sensitization: Geographic spread • Centrifugal spread • Referred pain • Bilateralization • (Primary and especially secondary somatosensory cortices send contralateral projections) • Generalized painMcCabe et al. Referred sensations in patients with complex regional pain syndrome type 1. Rheumatology (2003) Forss et al. Mirror-like spread of chronic pain. Neurology (2005)
    75. 75. Central Sensitization: Modality Effects • Allodynia • Variable quality • Cross-modality sensitization • Photophobia, acoustic sensitivity, etc. • Tendency to worsen with surgical or interventional procedures • Reduced opioid responsiveness • Opioid-induced hyperalgesiade Klaver et al. Hyperacusis in patients with complex regional pain syndrome related dystonia. J Neurol Neurosurg Psychiatr (2007) vol. 78 (12) pp. 1310-3
    76. 76. Central Sensitization: Temporal Effects• Persistence, longer after-sensations• Spontaneous, unpredictable exacerbations• DNIC reversal
    77. 77. Central Sensitization: Loss of DNIC• “Diffuse Noxious Inhibitory Controls”• Usually inhibit additional pain• Fail in chronic pain
    78. 78. Hormonal Effects: Stress Response • Hypothalamus - Pituitary - Adrenal • Cortisol • Neurotoxic • Metabolic changes • Depression, Anxiety • Thyroid, Growth Hormone, LH, FSH, ProlactinMäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Glucose regulation andchronic pain at multiple sites. Rheumatology (Oxford) 2008; 47, 1235-1238.Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Chronic pain, impairedglucose tolerance and diabetes: a community-based study. Pain 2008; 137,34-40.
    79. 79. Central Sensitization: Sympathetic System• Dysautonomia • Persistent hyperactivation • Paradoxical hyporeactivity to stress• Psychological
    80. 80. Central Sensitization: Autonomic Effects• Hyperhydrosis• Arousal/Non-arousal • Local Changes • Neurogenic edema• Loss of stsess-induced • Temperature changes hypoalgesia; onset of stress- induced hyperalgesia • Vascular changes • Trophic changes •Hair •Nails
    81. 81. Central Sensitization: Movement Effects • Difficulty in initiation, maintenance, and precision of small movements • Weakness • Dystonia • Decreased range of motion • Tremor • Spasm, myclonic jerks • Neglect-like syndromeSchwartzman et al. Pathophysiology of complex regional pain syndrome. Expert Rev. Neurotherapeutics (2006)
    82. 82. Central Sensitization: Systemic Effects• Sleep disturbance• Fatigue• Circadian Rhythm disruption• Development of Additional Pain Syndromes• Sickness Behavior
    83. 83. Central Sensitization: Psychological Effects • Augmented intrinsic effects • Cognitive/executive • Fear • Anger • Impulse • Social longing • Pain Behaviors • Motivation, helplessness effects • Depressive effects • Preoccupation with pain, body, self
    84. 84. Central Sensitization• Pain comes to dominate subjective experience, activity• Pain as pre-eminent psychic funnel, organizer, director
    85. 85. “Complexity,” Chaos, Dynamic Systems Theory: Sustaining Martinez-Lavin et al. Hypothesis: the chaos and complexity theory may help our understanding of fibromyalgia and similar maladies. Semin Arthritis Rheum (2008) vol. 37 (4) pp. 260-4
    86. 86. “Complexity,” Chaos, Dynamical System Theory: Sustaining• Nonlinearity• Self-organization• “Emergent” bifurcation• Phase transition• Strange Attraction• Fractal, self-similarity
    87. 87. “Complexity,” Chaos, Dynamical System Theory: Sustaining• Nonlinearity• Self-organization• “Emergent” bifurcation• Phase transition• Strange Attraction• Fractal, self-similarity
    88. 88. “Complexity,” Chaos, Dynamical System Theory: Sustaining• Nonlinearity• Self-organization• “Emergent” bifurcation• Phase transition• Strange Attraction• Fractal, self-similarity
    89. 89. “Complexity,” Chaos, Dynamical System Theory: Sustaining• Nonlinearity• Self-organization• “Emergent” bifurcation• Phase transition• Strange Attraction• Fractal, self-similarity
    90. 90. “Complexity,” Chaos, Dynamical System Theory: Sustaining• Nonlinearity• Self-organization• “Emergent” bifurcation• Phase transition• Strange Attraction• Fractal, self-similarity
    91. 91. Central Sensitization: Additional• Self Image• Trauma
    92. 92. Somatosensory Cortex • Homunculus • Routine persistence • Prominence of painful sites • Body Schema Lotze et al. Role of distorted body image in pain. Current rheumatology reports (2007) vol. 9 (6) pp. 488-96Elbert T et al. Reorganization of Flor et al. Extensive reorganization ofhuman cerebral cortex: the range of primary somatosensory cortex inchanges following use and injury. The chronic back pain patients. NeurosciNeuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8129-41 Schmidt-Wilcke et al. Affective Yang et al. Noninvasive detection of components and intensity of pain cerebral plasticity in adult human correlate with structural differences in somatosensory cortex. Neuroreport gray matter in chronic back pain (1994) vol. 5 (6) pp. 701-4 patients. Pain (2006) vol. 125 (1-2) pp. 89-97 Dykes. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can J Physiol Pharmacol (1997)
    93. 93. Somatosensory Cortex • Homunculus • Routine persistence • Prominence of painful sites • Body Schema Lotze et al. Role of distorted body image in pain. Current rheumatology reports (2007) vol. 9 (6) pp. 488-96Elbert T et al. Reorganization of Flor et al. Extensive reorganization ofhuman cerebral cortex: the range of primary somatosensory cortex inchanges following use and injury. The chronic back pain patients. NeurosciNeuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8129-41 Schmidt-Wilcke et al. Affective Yang et al. Noninvasive detection of components and intensity of pain cerebral plasticity in adult human correlate with structural differences in somatosensory cortex. Neuroreport gray matter in chronic back pain (1994) vol. 5 (6) pp. 701-4 patients. Pain (2006) vol. 125 (1-2) pp. 89-97 Dykes. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can J Physiol Pharmacol (1997)
    94. 94. Somatosensory Cortex • Homunculus • Routine persistence • Prominence of painful sites • Body Schema Lotze et al. Role of distorted body image in pain. Current rheumatology reports (2007) vol. 9 (6) pp. 488-96Elbert T et al. Reorganization of Flor et al. Extensive reorganization ofhuman cerebral cortex: the range of primary somatosensory cortex inchanges following use and injury. The chronic back pain patients. NeurosciNeuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8129-41 Schmidt-Wilcke et al. Affective Yang et al. Noninvasive detection of components and intensity of pain cerebral plasticity in adult human correlate with structural differences in somatosensory cortex. Neuroreport gray matter in chronic back pain (1994) vol. 5 (6) pp. 701-4 patients. Pain (2006) vol. 125 (1-2) pp. 89-97 Dykes. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can J Physiol Pharmacol (1997)
    95. 95. Somatosensory Cortex • Homunculus • Routine persistence • Prominence of painful sites • Body Schema Home > Marketplace > P 70 Products Department: Poste Lotze et al. Role of distorted body image in pain. Current rheumatology reports (2007) vol. 9 (6) pp. 488-96Elbert T et al. Reorganization of Flor et al. Extensive reorganization ofhuman cerebral cortex: the range of primary somatosensory cortex inchanges following use and injury. The chronic back pain patients. NeurosciNeuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8129-41 Schmidt-Wilcke et al. Affective Yang et al. Noninvasive detection of components and intensity of pain cerebral plasticity in adult human correlate with structural differences in somatosensory cortex. Neuroreport gray matter in chronic back pain From Sinister Wear (1994) vol. 5 (6) pp. 701-4 patients. Pain (2006) vol. 125 (1-2) pp. 89-97 JUMP TO SECTION: Dykes. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can J Physiol Pharmacol (1997)
    96. 96. Effects of Centralization: Change in self Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    97. 97. Effects of Centralization: Change in self• Change in body schema related to Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    98. 98. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    99. 99. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    100. 100. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation • intensity of stimulus Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    101. 101. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation • intensity of stimulus • attention to the stimulus Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    102. 102. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation • intensity of stimulus • attention to the stimulus• Change in body image Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    103. 103. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation • intensity of stimulus • attention to the stimulus• Change in body image• Change in self image Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    104. 104. Effects of Centralization: Change in self• Change in body schema related to • total amount of body surface stimulated (spatial summation) • temporal summation • intensity of stimulus • attention to the stimulus• Change in body image• Change in self image• Change in self Peyron et al. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiologie clinique = Clinical neurophysiology (2000) vol. 30 (5) pp. 263-88
    105. 105. Self, Identity Values Conscience Ego-Ideal Wished-for Self Self- Identifications Self- Confidence Esteem Gender Body Image Identity Self-Image IdentityThe ego is first and foremost a bodily ego....If we wish to find an anatomical analogy for it we can best identify itwith the “cortical homunculus” of the anatomists, which stands on its head in the cortex, sticks up its heels, facesbackwards and, as we know, has its speech-area on the left-hand side. -- Freud
    106. 106. Change in Self: Modified “Broken Selves” Robert S. Beal
    107. 107. Psychological TraumaGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during hospitalization. The Journal of burn car & rehabilitation (1994) vol. 15 (1) pp. 86-91; discussion 91-4
    108. 108. Psychological Trauma • Powerful Stimulus • Sensory • EmotionalGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during hospitalization. The Journal of burn car & rehabilitation (1994) vol. 15 (1) pp. 86-91; discussion 91-4
    109. 109. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • InescapableGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during hospitalization. The Journal of burn car & rehabilitation (1994) vol. 15 (1) pp. 86-91; discussion 91-4
    110. 110. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to CopeGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during hospitalization. The Journal of burn car & rehabilitation (1994) vol. 15 (1) pp. 86-91; discussion 91-4
    111. 111. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to Cope • Psychologically DamagingGilboa et al. The burn as a continuous traumatic stress: implications for emotional treatment during hospitalization. The Journal of burn car & rehabilitation (1994) vol. 15 (1) pp. 86-91; discussion 91-4
    112. 112. Chronic Pain as Continued Psychological Trauma • Inescapable Stimulus • Chronicity
    113. 113. Chronic Pain as Continued Psychological Trauma• Psychological load • augmented aversive effects, pain predominance, self image changes, secondary effects on personal and professional life • Lack of Control, Helplessness• Stimulus Barrier• Overwhelming• Inability to cope
    114. 114. Chronic Pain as Continued Psychological Trauma
    115. 115. Chronic Pain as Continued Psychological Trauma • Shame
    116. 116. Chronic Pain as Continued Psychological Trauma • Shame • Control
    117. 117. Chronic Pain as Continued Psychological Trauma • Shame • Control • Narcissistic mortification
    118. 118. Chronic Pain as Continued Psychological Trauma • Shame • Control • Narcissistic mortification • Guilt, self-blame
    119. 119. Chronic Pain as Continued Psychological Trauma
    120. 120. Chronic Pain as Continued Psychological Trauma • Regression
    121. 121. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations
    122. 122. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing
    123. 123. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse
    124. 124. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression
    125. 125. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism
    126. 126. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism • Loss
    127. 127. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism • Loss • Idiosyncratic meaning
    128. 128. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism • Loss • Idiosyncratic meaning • Nidus, amplifier for active conflicts
    129. 129. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism • Loss • Idiosyncratic meaning • Nidus, amplifier for active conflicts • Trauma reiterates prior trauma
    130. 130. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression • Primary and Secondary Narcissism • Loss • Idiosyncratic meaning • Nidus, amplifier for active conflicts • Trauma reiterates prior trauma • Potentiation of additional psychiatric syndromes
    131. 131. Title: Echoes Of Sadness Media: chalk on paper Chronic Pain as Continued Psychological Trauma Size: Artist: Origin: 17 inches long x 14 inches wide Maureen Brown Lakeland, Florida Artist Statem• Silent scream Damaging to “Self” reverberate r life. My sadn teardrop from • the other eye Loss of “Self” Black repetiti echoing pain in the forehea • tension, anxi Damaged “Self” feeling. • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    132. 132. %&(&)*$+",&-&.#&/"01+"1223 Chronic Pain as Continued Psychological Trauma I&?*8&J"G3C)$B*H/$)"+"8H,*H/$)*8&• Damaging to “Self” • E4.F0"G/&* Loss of “Self” L$M$)#*>$&3*+& • Damaged “Self” !"B")&*HC%&%I • M>"/&-&(8"=>)8) Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    133. 133. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    134. 134. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    135. 135. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    136. 136. +*81>?"*@>*A>)#"*B" (" Chronic Pain as Continued Psychological Trauma #$""C/&30"")* %&()*+$,"-./0.1#.("23,"2334 56 J.>+0.*K"H3>)$F*D/$)","8D,*D/$)*8& 5) (""*/00*&>9$F% 78 6+• C/&30"")* @ Damaging to “Self”A$N$)#*K$&3*+& • !"F")&*D>%&%G Loss of “Self” L="(.A.90"/=)0) ! • Damaged “Self” C 1 • 7 Broken “Self” ! • G Fragmented Self M8 • Unintegrated Self +*/1>?"*)>*0>)#"*."I* 8)5*6"/%*%$)F"*+*F/)Q&*L"0$"N"* +*/.*6"&*&3$%*0"%%"*."I* • Unstable Self +&*F/))>&*L"I* 8*5"/.7*+*%/6* +&Q%*R4%&*/*5"/.I* +Q.*&/N"0$)#*$)*%>."*1>05*4)%"")I* +*1$00*/1/?")*/)5*1$00*L"* &3"*9"%>)*+*>)F"*?)"1*/%*."I* S4&*6"/%*3/N"*9/%%"5* /)5*+7*&3"*%/."7*5$E& $)*&3$%*%&/)#"*&"%9/%%I* J>1*F/)*$&*0/%&T*
    137. 137. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    138. 138. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    139. 139. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    140. 140. Chronic Pain as Continued Psychological Trauma• Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
    141. 141. Chronic Pain: “Self” Conflict II• Inability to assimilate pain• Pain as foreign body, parasite• Unresolved
    142. 142. Chronic Pain: “Self” Conflict II• Inability to assimilate pain• Pain as foreign body, parasite• Unresolved
    143. 143. Chronic Pain: “Self” Conflict II• Inability to assimilate pain• Pain as foreign body, parasite• Unresolved
    144. 144. Central Sensitization: Summary of Psychological Effects • Amplification of aversive features • Pain as central focus, pre-eminent psychological organizer • Disrupts constructs of “self,” coerces new, conflicted constructs • Ongoing state of trauma

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