SOMATOSENSORY SYSTEMS AND PAIN
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1 SOMATOSENSORY SYSTEMS AND PAIN
2 A 21 year old man presented with a stab wound of the right side of the neck (Panel A). Neurological examination revealed right hemiplegia and complete right-sided loss of twopoint discrimination, proprioceptive and vibratory sensation below the level of C5. On the left side, the patient had a loss of pain and temperature sensation below the level of C7.
3 FEATURES OF THE BROWN SEQUARD SYNDROME: Ipsilateral loss of two point discrimation, conscious joint position sense, vibration sense Contralateral loss of pain and temperature Ipsilateral paralysis (with increased deep tendon reflexes)
4 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
5 MEDIAL-LEMNISCAL ANTEROLATERAL Dorsal columns Fast Neurons: place specific (topographic) Spinothalamic-spinoreticular Slow Neurons: larger receptive fields (Aδ vs C fiber pain) modality specific multimodal (parallel-labeled line) (highly convergent, except for periphery) Test: Test: two-point pain and temperature joint position sense vibration sensibility
6 SPECIFICITY IN THE SOMATOSENSORY PATHWAY IT BEGINS IN THE PERIPHERY
7 HAIRY SKIN HAIRLESS (GLABROUS) SKIN
8 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
9 REPRESENTATION OF THE BODY SURFACE IN THE POSTCENTRAL GYRUS
10 Magnification Factor
11 TWO-POINT DISCRIMINATION THRESHOLDS
12 REPRESENTATION OF THE BODY SURFACE IN THE POSTCENTRAL GYRUS How many maps?
13 Central sulcus CYTOARCHITECTURE OF THE POSTCENTRAL GYRUS
14 MULTIPLE MAPS IN THE POSTCENTRAL GYRUS AREA 3b OWL MONKEY AREA 1
15
16
17 VIBRISSA-INDUCED GLUCOSE UTILIZATION IN RAT SOMATOSENSORY CORTEX ONE VIBRISSA----ONE CORTICAL COLUMN
18 USE IT OR LOSE IT BRAILLE AMPUTATION
19
20 PAIN
21 PAIN IS A SUBJECTIVE EXPERIENCE: It is not a stimulus MAJOR FEATURES OF THE PAIN EXPERIENCE: Sensory discriminative Affective (emotional) Cognitive MEASUREMENT OF PAIN: A BIG PROBLEM
22 Worst pain ever Visual Analogue Scale (VAS) No pain
23 O U C H E R S C A L E
24 DESCARTES
25 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
26 DESCARTES
27 ANTEROLATERAL CORDOTOMY (SPINOTHALAMIC TRACTOTOMY)
28 NEUROSURGICAL PROCEDURES THAT HAVE BEEN USED TO TREAT PAIN
29 NOCICEPTIVE (TISSUE INJURY) PAIN: (Associated with inflammation) Aches and sprains Back pain Arthritis Temporomandibular joint pain (TMD) Cancer Headache (migraine)
30 Nociceptive Pain: Tissue Injury/Inflammation
31 NEUROPATHIC (NERVE INJURY) PAIN: Reflex sympathetic dystrophy (RSD); causalgia Trigeminal Neuralgia Post-herpetic neuralgia Anesthesia Dolorosa Phantom Limb Pain Cancer
32 Neuropathic Pain: Nerve Injury (RSD)
33 Neuropathic Pain: Post-Herpetic Neuralgia
34
35 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract ----IS NOT A PAIN TRACT
36 So where does specificity break down?
37 Peripheral nerves contain small and large diameter primary afferent fibers
38 Large myelinated Aβ Small myelinated Aδ Unmyelinated C Peripheral nerve fibers
39
40 Myelinated A delta and unmyelinated C fibers only respond to noxious stimulation
41 But in the setting of tissue injury the small diameter fibers respond to innocuous stimulation: NON-PAINFUL STIMULI NOW HURT!
42 Tissue Injury Arachidonic acid Cyclooxygenase Prostaglandins C FIBER THRESHOLD LOWERED ALLODYNIA PERIPHERAL SENSITIZATION
43 NSAIDS Aspirin Ibuprofen Naprosyn (Alleve) Cox-2 inhibitors
44 Large myelinated afferents (Aβ) do not respond to noxious stimulation
45 But activity of large diameter fibers can reduce the pain that results from activity in small diameter primary afferent fibers. SHAKE YOUR HAND; IT HURTS LESS!
46 Organization of the Dorsal Horn Laminar organization
47
48
49 Organization of the Dorsal Horn Somatic-visceral convergence: Referred Pain
50
51 REFERRED PAIN
52
53 Organization of the Dorsal Horn CENTRAL SENSITIZATION
54 Central sensitization: Tissue Damage Nerve Injury
55 Central sensitization:
56 CENTRAL SENSITIZATION Pain responsive neurons can now be activated by non-noxious stimuli (allodynia) Receptive field size of dorsal horn neuron increases Spontaneous activity increases
57 Mechanisms of Central Sensitization C-fiber input NMDA Mg ++ NK-1 AMPA WDR cell
58 Mechanisms of Central Sensitization Presynaptic: Increased transmitter release Ca 2+ MOR C-fiber input Gabapentin (α2δ) Ziconatide (N) Morphine Prostaglandin (EP receptor) COX inhibitors
59 Mechanisms of Central Sensitization Presynaptic: Increased transmitter release Ca 2+ MOR C-fiber input Prostaglandin (EP receptor) NMDA AMPA Postsynaptic: increased response to transmitter strengthening of synaptic efficacy Mg ++ ALTERATION IN SECOND MESSENGERS PHOSPHORYLATION OF RECEPTORS AND ION CHANNELS WDR cell INCREASED EXCITABILITY AND SYNAPTIC EFFICACY
60 Mechanisms of Central Sensitization: Descending influences Facilitation Inhibition (SNRI) 5-HT and NE Glutamate GABA (Anticonvuslants) Glycine
61 Microglia Quiescent glia Ipsi Contra Nerve injury Activated glia
62 Organization of the Dorsal Horn Ascending pathways
63 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
64 Dimensions of Pain Perception Sensory-Discriminative Stimulus features: Location, Modality, Intensity Affective-Motivational How unpleasant or upsetting is the pain? What will I do about the pain?
65 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
66 Nociceptive neurons in lateral, medial and posterior thalamus
67 Somatosensory cortex
68 Pain activates sensory cortex S1 S2
69 Somatosensory cortex Anterior cingulate cortex Insular cortex
70 Pain activates limbic cortex ACC IC
71 Pain affect without pain sensation in patient with postcentral lesion (Ploner et al. 1999)
72 Where pain activity in the brain is evoked depends on. what part of the body was stimulated.
73 Esophageal distension vs noxious thermal heat Insular Cortex QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Motor Cortex Anterior Cingulate Cortex Strigo, I. A. Bushnell, M. C. Alert
74 It depends on. who was stimulated.
75 QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Male Female From Casey et al
76 It depends on. the psychological state of the subject when he/she was stimulated.
77 It depends on. how much attention is paid to the stimulus.
78 Pain evokes more brain activity when attending to pain Attention to pain Attention to tones Bushnell et al. 1999
79 It depends on. how much pain you expect to experience.
80 Expectancy can alter pain Pain Warm Warm (expect pain) (expect pain) (expect warm) Sawamoto et al. 2000
81 It depends on. the meaning (and emotional content) of the stimulus.
82 What can we conclude.. There is no pain area in the brain. Rather, a matrix of activity in loci related to cognitive, affective and sensorydiscriminative components underlies the overall pain experience.
83 What can we conclude...that you cannot predict and must never assume that you know the magnitude and quality of pain that people experience.
84 PAIN CONTROL
85 PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen; COX-2 inhibitors) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis
86 DEEP BRAIN STIMULATION
87 DEEP BRAIN STIMULATION MODULATION NALOXONE OPIATES + Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
88 ENDORPHINS Enkephalin Dynorphin β Endorphin Opioid Receptors NALOXONE
89 PAG stimulation evokes the MODULATION release of endorphins to initiate descending inhibition and pain OPIATES control NALOXONE is the key to this interpretation. DEEP BRAIN STIMULATION Periaqueductal Gray (PAG) Nucleus Raphe Magnus (NRM) Dorsal horn
90 ENDORPHINS Enkephalin Dynorphin β Endorphin Endogenous Opioid Receptors Exogenous Morphine and other opiates
91 SIDE EFFECTS MODULATION OPIATES SYSTEMIC MORPHINE OPIATE ANALGESIA Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn GUT (CONSTIPATION)
92 OPIATE ANALGESIA MODULATION OPIATES EPIDURAL MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
93 MORPHINE
94 PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis
95 S1 ACC Under Hypnosis Rainville et al HIGH Unpleasantness LOW
San Francisco Chronicle, June 2001
PAIN San Francisco Chronicle, June 2001 CONGENITAL INSENSITIVITY TO PAIN PAIN IS A SUBJECTIVE EXPERIENCE: It is not a stimulus MAJOR FEATURES OF THE PAIN EXPERIENCE: Sensory discriminative Affective (emotional)
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