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

4. Pain Afferents

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

31. Neuroanatomic Spreading

32. Neuroanatomic Spreading

33. Neuroanatomic Spreading

34. Neuroanatomic Spreading

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
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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
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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
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• Fragmented Self
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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

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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