San Francisco Chronicle, June 2001
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1 PAIN
2 San Francisco Chronicle, June 2001
3 CONGENITAL INSENSITIVITY TO PAIN
4 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
5 Worst pain ever Visual Analogue Scale (VAS) No pain
6 O U C H E R S C A L E
7 DESCARTES
8 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
9 DESCARTES
10 ANTEROLATERAL CORDOTOMY (SPINOTHALAMIC TRACTOTOMY)
11 NEUROSURGICAL PROCEDURES THAT HAVE BEEN USED TO TREAT PAIN
12 NOCICEPTIVE (TISSUE INJURY) PAIN: (Associated with inflammation) Aches and sprains Back pain Arthritis Temporomandibular joint pain (TMD) Cancer Headache (migraine) Allodynia and hyperalgesia
13 Nociceptive Pain: Tissue Injury/Inflammation
14 NEUROPATHIC (NERVE INJURY) PAIN: Reflex sympathetic dystrophy (RSD); causalgia Trigeminal Neuralgia Post-herpetic neuralgia Anesthesia Dolorosa Phantom Limb Pain Cancer
15 Neuropathic Pain: Nerve Injury (RSD)
16 Neuropathic Pain: Post-Herpetic Neuralgia
17
18 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract ----IS NOT A PAIN TRACT
19 So where does specificity break down?
20 Peripheral nerves contain small and large diameter primary afferent fibers
21 Myelinated A delta and unmyelinated C fibers only respond to noxious stimulation
22 But in the setting of tissue injury the small diameter fibers respond to innocuous stimulation: NON-PAINFUL STIMULI NOW HURT!
23 Tissue Injury Arachidonic acid Cyclooxygenase Prostaglandins C FIBER THRESHOLD LOWERED ALLODYNIA PERIPHERAL SENSITIZATION
24 NSAIDS Aspirin Ibuprofen Naprosyn (Alleve) Cox-2 inhibitors
25 Large myelinated afferents (A ) do not respond to noxious stimulation
26 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!
27 Organization of the Dorsal Horn Laminar organization
28
29
30 Organization of the Dorsal Horn Somatic-visceral convergence: Referred Pain
31
32 REFERRED PAIN
33 Organization of the Dorsal Horn CENTRAL SENSITIZATION
34 Central sensitization: Tissue Damage Nerve Injury
35 Central sensitization:
36 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
37 Mechanisms of Central Sensitization Presynaptic: Increased transmitter release 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
38 And still more contributors to central sensitization
39 Mechanisms of Central Sensitization: Descending influences Facilitation Inhibition (SNRI) 5-HT and NE Glutamate GABA (Anticonvuslants) Glycine
40 And neurons are no longer the only target: The contribution of glia
41 Microglia Quiescent glia Ipsi Contra Nerve injury Activated glia
42 Organization of the Dorsal Horn Ascending pathways
43 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
44 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?
45 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
46 Nociceptive neurons in lateral, medial and posterior thalamus
47 Somatosensory cortex
48 Pain activates sensory cortex S1 S2
49 Somatosensory cortex Anterior cingulate cortex Insular cortex
50 Pain activates limbic cortex ACC IC
51 Pain affect without pain sensation in patient with postcentral lesion (Ploner et al. 1999)
52 But exactly where and to what extent? It depends.
53 It depends on. what part of the body was stimulated.
54 Esophageal distension vs noxious thermal heat Insular Cortex QuickTime and a TIFF (Uncompressed) decompressor are needed to see t his picture. Motor Cortex Anterior Cingulate Cortex Strigo, I. A. Bushnell, M. C. Alert
55 It depends on. who was stimulated.
56 QuickTime and a TIFF (Uncompress ed) decompressor are needed to see this picture. Male Female From Casey et al
57 It depends on. how much attention is paid to the stimulus.
58 Pain evokes more brain activity when attending to pain Attention to pain Attention to tones Bushnell et al. 1999
59 It depends on. how much pain you expect to experience.
60 Expectancy can alter pain Pain Warm Warm (expect pain) (expect pain) (expect warm) Sawamoto et al. 2000
61 PAIN CONTROL
62 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
63 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
64 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
65 DEEP BRAIN STIMULATION
66 DEEP BRAIN STIMULATION MODULATION NALOXONE OPIATES + - Dorsal Periaqueductal Gray Nucleus Raphe Magnus horn
67 ENDORPHINS Enkephalin Dynorphin Endorphin Opioid Receptors NALOXONE
68 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
69 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
70 ENDORPHINS Enkephalin Dynorphin Endorphin Endogenous Opioid Receptors Exogenous Morphine and other opiates
71 OPIATE ANALGESIA MODULATION OPIATES SYSTEMIC MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
72 SIDE EFFECTS MODULATION OPIATES SYSTEMIC MORPHINE OPIATE ANALGESIA Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn GUT (CONSTIPATION)
73 OPIATE ANALGESIA MODULATION OPIATES EPIDURAL MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
74 MORPHINE
75 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
76 S1 Rainville et al 1997 Before Hypnosis ACC Rainville et al High Unpleasantness
77 S1 ACC Under Hypnosis Rainville et al HIGH Unpleasantness LOW
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