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Central Sensitization In Chronic Pain

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Central Sensitization © Matthew B. Smith, 2010 Matthew B. Smith, M.D. Faculty, NYU School of Medicine General Adult psychiatry Liaison Psychiatrist, NYU Pain Management Team Liaison Psychiatrist, NYU Palliative Care Team
Central Sensitization: Outline • General • Plasticity • Pain Matrix • Clinical and Secondary • Complexity Theory • Psychological Effects
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 • Unmyelinated • Large • Small • Pressure, heat • Polymodal
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)
Peripheral Sensitization Giordano. The neurobiology of nociceptive and anti-nociceptive systems. Pain physician (2005) vol. 8 (3) pp. 277-90
Central Sensitization: Neuronal Plasticity • Synaptic plasticity: Hebbian • Non-Hebbian Plasticity
Synaptic Plasticity: Hebbian Theory •Hebb DO. 1949. The Organization of Behavior; A Neuropsychological Theory. New York: Wiley. xix, 335 pp.
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.
• Strong Afferent Stimulation
Synaptic Plasticity: LTP • Strong Afferent Stimulation
Synaptic Plasticity: LTP KEGG 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
Synaptic Plasticity: LTP KEGG 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
Synaptic Plasticity: LTP KEGG 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
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 presynaptic neurons)
LTP: Temporal Summation (Kindling, Windup) 1 2 3 4 5 6 (Also, spatial summation -- from different presynaptic neurons)
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 Anterior Cingulate Cortex G Table 1. Long-term potentiation (LTP) recorded from sensory- A related central synapses. Induction protocol LTP Prefrontal 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 ND Periaqueductal gray (PAG) ND ND Rostroventral 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-
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
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 PM Long-term depression - Homo sapiens (human) [ Pathway menu | Reference list ] Homo sapiens (human) Go Current selection
Neuroanatomic Spreading
Neuroanatomic Spreading
Neuroanatomic Spreading
Neuroanatomic Spreading
Ephaptic Crosstalk ephapse A place where two or more nerve cell processes (axons, dendrites) touch without forming a typical synaptic contact
Changes with Neuronal Plasticity in Chronic • Morphologic • Neurochemical • Immunologic • Neuronal loss • Sensory Processing
Morphologic Changes in Neuronal Plasticity • Axonal sprouting and pruning • Dendritic sprouting and pruning Goldin et al. Functional plasticity triggers formation and pruning of dendritic spines in cultured hippocampal networks. J Neurosci (2001) vol. 21 (1) pp. 186-93 Engert 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
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
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
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
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. 4004-7 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
Sensory Processing: Deafferentation, Allodynia Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
Melzack: Gate Control Theory - P---- LUJi;lllVI;L WILIIUM b- ,iort fibers and by the toagr of Lissauer's 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 shown lleys of nerve impulses in large are extremely effective initially vating' the T cells but that their ffect is reduced by a negative ck 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 substantia ck 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 by ect 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 the ane potential of the afferent erminals 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
Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways
Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus Dorsal Horn
Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
Central Sensitization: Spinothalamic Tracts, Pain Amplification Thalamus Hypothalamus Septum VTA Amygdala PAG Sympathetic Magnocellular Nucleus Dorsal Horn
Central Sensitization: Spinothalamic Tracts, Pain Amplification • Hypothalamus: • Amygdala: Fear, • PAG: Motivation Stress, Sympathetic Motivation • VTA: Motivation, • Septum: Emotion, Movement Motivation Thalamus Hypothalamus Septum VTA Amygdala PAG Sympathetic Magnocellular Nucleus Dorsal Horn
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
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
Pain Matrix Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
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
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
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
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
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
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
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
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
Central Sensitization: Additional and Clinical Aspects • Secondary hyperalgesia • Geographic Spread • Modality effects • Temporal effects • Stress • Autonomic effects • Movement effects • Systemic effects • Psychological effects
Central Sensitization: Secondary Hyperalgesia • Reduced threshold • Hyperpathia • Paresthesia • Numbness
Central Sensitization: Geographic spread • Centrifugal spread • Referred pain • Bilateralization • (Primary and especially secondary somatosensory cortices send contralateral projections) • Generalized pain McCabe 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)
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 hyperalgesia de Klaver et al. Hyperacusis in patients with complex regional pain syndrome related dystonia. J Neurol Neurosurg Psychiatr (2007) vol. 78 (12) pp. 1310-3
Central Sensitization: Temporal Effects • Persistence, longer after-sensations • Spontaneous, unpredictable exacerbations • DNIC reversal
Central Sensitization: Loss of DNIC • “Diffuse Noxious Inhibitory Controls” • Usually inhibit additional pain • Fail in chronic pain
Hormonal Effects: Stress Response • Hypothalamus - Pituitary - Adrenal • Cortisol • Neurotoxic • Metabolic changes • Depression, Anxiety • Thyroid, Growth Hormone, LH, FSH, Prolactin Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Glucose regulation and chronic pain at multiple sites. Rheumatology (Oxford) 2008; 47, 1235-1238. Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Chronic pain, impaired glucose tolerance and diabetes: a community-based study. Pain 2008; 137, 34-40.
Central Sensitization: Sympathetic System • Dysautonomia • Persistent hyperactivation • Paradoxical hyporeactivity to stress • Psychological
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
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 syndrome Schwartzman et al. Pathophysiology of complex regional pain syndrome. Expert Rev. Neurotherapeutics (2006)
Central Sensitization: Systemic Effects • Sleep disturbance • Fatigue • Circadian Rhythm disruption • Development of Additional Pain Syndromes • Sickness Behavior
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
Central Sensitization • Pain comes to dominate subjective experience, activity • Pain as pre-eminent psychic funnel, organizer, director
“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
“Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
“Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
“Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
“Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
“Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
Central Sensitization: Additional • Self Image • Trauma
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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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)
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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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)
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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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)
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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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)
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
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
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
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
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
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
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
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
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
Self, Identity Values Conscience Ego-Ideal Wished-for Self Self- Identifications Self- Confidence Esteem Gender Body Image Identity Self-Image Identity The ego is first and foremost a bodily ego....If we wish to find an anatomical analogy for it we can best identify it with the “cortical homunculus” of the anatomists, which stands on its head in the cortex, sticks up its heels, faces backwards and, as we know, has its speech-area on the left-hand side. -- Freud
Change in Self: Modified “Broken Selves” Robert S. Beal
Psychological Trauma Gilboa 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
Psychological Trauma • Powerful Stimulus • Sensory • Emotional Gilboa 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
Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable Gilboa 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
Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to Cope Gilboa 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
Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to Cope • Psychologically Damaging Gilboa 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
Chronic Pain as Continued Psychological Trauma • Inescapable Stimulus • Chronicity
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
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 • Dependent: longing for soothing, nurturing
Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse
Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression
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
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
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
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
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
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
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
%&'(&)'*$+",&-&.#&/"01+"1223 Chronic Pain as Continued Psychological Trauma I&?*8&'J"G3'C)$B*H/$)"+"8H,*H/$)*8'& • Damaging to “Self” • E4.F0"G/&* Loss of “Self” L$M$)#*>$&3*+& • Damaged “Self” !"B")&*HC%&%I • M>"/&-&(8"=>)8) Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
+*81>?"*@>*A>)#"'*B" (" Chronic Pain as Continued Psychological Trauma #$""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*
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
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 focus, pre-eminent psychological organizer • Disrupts constructs of “self,” coerces new, conflicted constructs • Ongoing state of trauma

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Central Sensitization In Chronic Pain

  • 1. Central Sensitization © Matthew B. Smith, 2010 Matthew B. Smith, M.D. Faculty, NYU School of Medicine General Adult psychiatry Liaison Psychiatrist, NYU Pain Management Team Liaison Psychiatrist, NYU Palliative Care Team
  • 2. Central Sensitization: Outline • General • Plasticity • Pain Matrix • Clinical and Secondary • Complexity Theory • Psychological Effects
  • 3. Definitions: Acute Pain, Chronic Pain • Time • 3-6 months • Mechanism • Central Sensitization
  • 5. Pain Afferents • A-delta fibers • First pain • Myelinated • Large • Pressure, heat
  • 6. Pain Afferents • A-delta fibers • C fibers • First pain • Second pain • Myelinated • Unmyelinated • Large • Small • Pressure, heat • Polymodal
  • 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. Peripheral Sensitization Giordano. The neurobiology of nociceptive and anti-nociceptive systems. Pain physician (2005) vol. 8 (3) pp. 277-90
  • 9. Central Sensitization: Neuronal Plasticity • Synaptic plasticity: Hebbian • Non-Hebbian Plasticity
  • 10. Synaptic Plasticity: Hebbian Theory •Hebb DO. 1949. The Organization of Behavior; A Neuropsychological Theory. New York: Wiley. xix, 335 pp.
  • 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. • Strong Afferent Stimulation
  • 13. Synaptic Plasticity: LTP • Strong Afferent Stimulation
  • 14. Synaptic Plasticity: LTP KEGG 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. Synaptic Plasticity: LTP KEGG 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. Synaptic Plasticity: LTP KEGG 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. LTP: Temporal Summation (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
  • 18. LTP: Temporal Summation (Kindling, Windup) (Also, spatial summation -- from different presynaptic neurons)
  • 19. LTP: Temporal Summation (Kindling, Windup) 1 2 3 4 (Also, spatial summation -- from different presynaptic neurons)
  • 20. LTP: Temporal Summation (Kindling, Windup) 1 2 3 4 5 6 (Also, spatial summation -- from different presynaptic neurons)
  • 21. LTP: Post-Tetanic Facilitation
  • 22. LTP: Post-Tetanic Facilitation
  • 23. LTP: Post-Tetanic Facilitation
  • 24. LTP: Post-Tetanic Facilitation
  • 25. LTP: Post-Tetanic Facilitation
  • 26. LTP: Spike timing dependent plasticity, concidence .05 msec
  • 27. 260 LTP: Regional Variation A Synaptic Model for Pain: Long-Term Potentiation in the Anterior Cingulate Cortex G Table 1. Long-term potentiation (LTP) recorded from sensory- A related central synapses. Induction protocol LTP Prefrontal 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 ND Periaqueductal gray (PAG) ND ND Rostroventral 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. 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. Non-Hebbian Neuronal Plasticity • Long-term Depression • Neuroanatomic spreading • Ephaptic Crosstalk
  • 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
  • 35. Ephaptic Crosstalk ephapse A place where two or more nerve cell processes (axons, dendrites) touch without forming a typical synaptic contact
  • 36. Changes with Neuronal Plasticity in Chronic • Morphologic • Neurochemical • Immunologic • Neuronal loss • Sensory Processing
  • 37. Morphologic Changes in Neuronal Plasticity • Axonal sprouting and pruning • Dendritic sprouting and pruning Goldin et al. Functional plasticity triggers formation and pruning of dendritic spines in cultured hippocampal networks. J Neurosci (2001) vol. 21 (1) pp. 186-93 Engert 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. 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. 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. 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. 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. 4004-7 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
  • 42. Sensory Processing: Deafferentation, Allodynia Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 43. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 44. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 45. Sensory Processing: Deafferentation, Allodynia Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 46. Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 47. Sensory Processing: Deafferentation, Allodynia Touch Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 48. Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 49. Sensory Processing: Deafferentation, Allodynia Primary Pain Afferent Primary Pain Dorsal Horn Afferent Woolf et al. The pathophysiology of chronic pain--increased sensitivity to low threshold A beta-fibre inputs. Curr Opin Neurobiol (1994)
  • 50. Melzack: Gate Control Theory - P---- LUJi;lllVI;L WILIIUM b- ,iort fibers and by the toagr of Lissauer's 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 shown lleys of nerve impulses in large are extremely effective initially vating' the T cells but that their ffect is reduced by a negative ck 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 substantia ck 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 by ect 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 the ane potential of the afferent erminals 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. Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways
  • 52. Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus Dorsal Horn
  • 53. Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
  • 54. Central Sensitization: Spinothalamic Tracts, Pain Amplification • Descending Modulatory Pathways Thalamus PAG Magnocellular Nucleus Locus Ceruleus Raphe Nucleus Dorsal Horn
  • 55. Central Sensitization: Spinothalamic Tracts, Pain Amplification Thalamus Hypothalamus Septum VTA Amygdala PAG Sympathetic Magnocellular Nucleus Dorsal Horn
  • 56. Central Sensitization: Spinothalamic Tracts, Pain Amplification • Hypothalamus: • Amygdala: Fear, • PAG: Motivation Stress, Sympathetic Motivation • VTA: Motivation, • Septum: Emotion, Movement Motivation Thalamus Hypothalamus Septum VTA Amygdala PAG Sympathetic Magnocellular Nucleus Dorsal Horn
  • 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. 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. Pain Matrix Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
  • 60. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
  • 61. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
  • 62. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
  • 63. Pain Matrix Prefrontal Somatosensory Cingulate Cortex Cortex Cortex Basal Ganglia Amygdala Insula Thalamus Brainstem Hippocammpus PAG Spinal Cord Jones et al. Pain mechanisms and their disorders. Br Med Bull (2003) vol. 65 pp. 83-93
  • 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. 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. 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. 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. 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. 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. 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. 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. Central Sensitization: Additional and Clinical Aspects • Secondary hyperalgesia • Geographic Spread • Modality effects • Temporal effects • Stress • Autonomic effects • Movement effects • Systemic effects • Psychological effects
  • 73. Central Sensitization: Secondary Hyperalgesia • Reduced threshold • Hyperpathia • Paresthesia • Numbness
  • 74. Central Sensitization: Geographic spread • Centrifugal spread • Referred pain • Bilateralization • (Primary and especially secondary somatosensory cortices send contralateral projections) • Generalized pain McCabe 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. 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 hyperalgesia de 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. Central Sensitization: Temporal Effects • Persistence, longer after-sensations • Spontaneous, unpredictable exacerbations • DNIC reversal
  • 77. Central Sensitization: Loss of DNIC • “Diffuse Noxious Inhibitory Controls” • Usually inhibit additional pain • Fail in chronic pain
  • 78. Hormonal Effects: Stress Response • Hypothalamus - Pituitary - Adrenal • Cortisol • Neurotoxic • Metabolic changes • Depression, Anxiety • Thyroid, Growth Hormone, LH, FSH, Prolactin Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Glucose regulation and chronic pain at multiple sites. Rheumatology (Oxford) 2008; 47, 1235-1238. Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Chronic pain, impaired glucose tolerance and diabetes: a community-based study. Pain 2008; 137, 34-40.
  • 79. Central Sensitization: Sympathetic System • Dysautonomia • Persistent hyperactivation • Paradoxical hyporeactivity to stress • Psychological
  • 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. 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 syndrome Schwartzman et al. Pathophysiology of complex regional pain syndrome. Expert Rev. Neurotherapeutics (2006)
  • 82. Central Sensitization: Systemic Effects • Sleep disturbance • Fatigue • Circadian Rhythm disruption • Development of Additional Pain Syndromes • Sickness Behavior
  • 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. Central Sensitization • Pain comes to dominate subjective experience, activity • Pain as pre-eminent psychic funnel, organizer, director
  • 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. “Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
  • 87. “Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
  • 88. “Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
  • 89. “Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
  • 90. “Complexity,” Chaos, Dynamical System Theory: Sustaining • Nonlinearity • Self-organization • “Emergent” bifurcation • Phase transition • Strange Attraction • Fractal, self-similarity
  • 91. Central Sensitization: Additional • Self Image • Trauma
  • 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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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. 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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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. 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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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. 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. 488-96 Elbert T et al. Reorganization of Flor et al. Extensive reorganization of human cerebral cortex: the range of primary somatosensory cortex in changes following use and injury. The chronic back pain patients. Neurosci Neuroscientist (2004) vol. 10 (2) pp. Lett (1997) vol. 224 (1) pp. 5-8 129-41 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Self, Identity Values Conscience Ego-Ideal Wished-for Self Self- Identifications Self- Confidence Esteem Gender Body Image Identity Self-Image Identity The ego is first and foremost a bodily ego....If we wish to find an anatomical analogy for it we can best identify it with the “cortical homunculus” of the anatomists, which stands on its head in the cortex, sticks up its heels, faces backwards and, as we know, has its speech-area on the left-hand side. -- Freud
  • 106. Change in Self: Modified “Broken Selves” Robert S. Beal
  • 107. Psychological Trauma Gilboa 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. Psychological Trauma • Powerful Stimulus • Sensory • Emotional Gilboa 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. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable Gilboa 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. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to Cope Gilboa 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. Psychological Trauma • Powerful Stimulus • Sensory • Emotional • Inescapable • Overwhelming • Inability to Cope • Psychologically Damaging Gilboa 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. Chronic Pain as Continued Psychological Trauma • Inescapable Stimulus • Chronicity
  • 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. Chronic Pain as Continued Psychological Trauma
  • 115. Chronic Pain as Continued Psychological Trauma • Shame
  • 116. Chronic Pain as Continued Psychological Trauma • Shame • Control
  • 117. Chronic Pain as Continued Psychological Trauma • Shame • Control • Narcissistic mortification
  • 118. Chronic Pain as Continued Psychological Trauma • Shame • Control • Narcissistic mortification • Guilt, self-blame
  • 119. Chronic Pain as Continued Psychological Trauma
  • 120. Chronic Pain as Continued Psychological Trauma • Regression
  • 121. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations
  • 122. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing
  • 123. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse
  • 124. Chronic Pain as Continued Psychological Trauma • Regression • Primitive Object Relations • Dependent: longing for soothing, nurturing • Experiencing deprivation, abuse • Struggle against regression
  • 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. 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. 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. 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. 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. 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. 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. %&'(&)'*$+",&-&.#&/"01+"1223 Chronic Pain as Continued Psychological Trauma I&?*8&'J"G3'C)$B*H/$)"+"8H,*H/$)*8'& • Damaging to “Self” • E4.F0"G/&* Loss of “Self” L$M$)#*>$&3*+& • Damaged “Self” !"B")&*HC%&%I • M>"/&-&(8"=>)8) Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 133. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 134. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 135. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 136. +*81>?"*@>*A>)#"'*B" (" Chronic Pain as Continued Psychological Trauma #$""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. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 138. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 139. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 140. Chronic Pain as Continued Psychological Trauma • Damaging to “Self” • Loss of “Self” • Damaged “Self” • Broken “Self” • Fragmented Self • Unintegrated Self • Unstable Self
  • 141. Chronic Pain: “Self” Conflict II • Inability to assimilate pain • Pain as foreign body, parasite • Unresolved
  • 142. Chronic Pain: “Self” Conflict II • Inability to assimilate pain • Pain as foreign body, parasite • Unresolved
  • 143. Chronic Pain: “Self” Conflict II • Inability to assimilate pain • Pain as foreign body, parasite • Unresolved
  • 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

Notes de l'éditeur

  1. 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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  126. 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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  147. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  148. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  149. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  150. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  151. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  152. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  153. Now, pain is no longer a recurrent experience that the self has; rather pain is a part of the self. Is now introjected. \n
  154. 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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  156. \n
  157. Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  158. Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  159. Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  160. Why this psychobabble theory? \nDistinguish from \npsychobabble\ntrauma of post-traumatic stress disorder \n\n
  161. 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
  162. 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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  167. 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
  168. 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
  169. 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
  170. 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
  171. 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
  172. 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
  173. 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
  174. 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
  175. 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
  176. 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
  177. 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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