PAIN IS A SUBJECTIVE EXPERIENCE: It is not a stimulus. MAJOR FEATURES OF THE PAIN EXPERIENCE: Sensory discriminative Affective (emotional) Cognitive

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1 PAIN

2 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

3 Worst pain ever Visual Analogue Scale (VAS) No pain

4 O U C H E R S C A L E

5 DESCARTES

6 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

7 DESCARTES

8 ANTEROLATERAL CORDOTOMY (SPINOTHALAMIC TRACTOTOMY)

9 NEUROSURGICAL PROCEDURES THAT HAVE BEEN USED TO TREAT PAIN

10 NOCICEPTIVE (TISSUE INJURY) PAIN: (Associated with inflammation) Aches and sprains Back pain Arthritis Temporomandibular joint pain (TMD) Cancer Headache (migraine) Allodynia and hyperalgesia

11 Nociceptive Pain: Tissue Injury/Inflammation

12 NEUROPATHIC (NERVE INJURY) PAIN: RSD; causalgia; CRPS Trigeminal Neuralgia Post-herpetic neuralgia Anesthesia Dolorosa Phantom Limb Pain Cancer

13 Neuropathic Pain: Nerve Injury (RSD)

14

15 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract ----IS NOT A PAIN TRACT

16 So where and how does the specificity break down?

17 Peripheral nerves contain small and large diameter primary afferent fibers

18 Large myelinated Ab Small myelinated Ad Unmyelinated C Peripheral nerve fibers

19 Myelinated A delta and unmyelinated C fibers only respond to noxious stimulation

20

21 But in the setting of tissue injury the small diameter fibers respond to innocuous stimulation: NON-PAINFUL STIMULI NOW HURT!

22 Tissue Injury Arachidonic acid Cyclooxygenase Prostaglandins C FIBER THRESHOLD LOWERED ALLODYNIA PERIPHERAL SENSITIZATION

23 NSAIDS Aspirin Ibuprofen Naprosyn (Alleve) Cox-2 inhibitors

24 Even this picture is over simplified: Nociceptors (C fibers) are not homogeneous

25 Transducers in nociceptors Schulz and Woolf Na + channels (1.7)

26 Large myelinated afferents (Ab) do not respond to noxious stimulation

27 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!

28 And loss of large fibers mimics peripheral neuropathic pain conditions

29 Small pain fibers Large non-pain fibers QuickTime and a DV - NTSC decompressor are needed to see this picture.

30 A beta s and C s excite PTN neurons GABAergic interneuron Pain transmission neuron A beta s also inhibit, via inhibitory interneurons

31 Organization of the dorsal horn Laminar organization

32

33 Organization of the dorsal horn Somatic-visceral convergence: Referred Pain

34 REFERRED PAIN

35

36 Organization of the Dorsal Horn Ascending pathways

37 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

38 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?

39 Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

40 Nociceptive neurons in lateral, medial and posterior thalamus

41 Somatosensory cortex

42 Pain activates sensory cortex S1 S2

43 Somatosensory cortex Anterior cingulate cortex Insular cortex

44 Pain activates limbic cortex ACC IC

45 Pain affect without pain sensation in patient with postcentral lesion (Ploner et al. 1999)

46 Measuring the affective component of the pain experience in animals

47 But exactly where in the brain is pain and to what extent? It depends.

48 It depends on. what part of the body was stimulated.

49 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

50 It depends on. who was stimulated.

51 QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Male Female From Casey et al

52 It depends on. the psychological state of the subject when he/she was stimulated.

53 It depends on. how much attention is paid to the stimulus.

54 Pain evokes more brain activity when attending to pain Attention to pain Attention to tones Bushnell et al. 1999

55 It depends on. how much pain you expect to experience.

56 Expectancy can alter pain Pain Warm Warm (expect pain) (expect pain) (expect warm) Sawamoto et al. 2000

57 It depends on. the meaning (and emotional content) of the stimulus.

58 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.

59 What can we conclude...that you cannot predict and must never assume that you know the magnitude and quality of pain that people experience.

60 PAIN CONTROL

61 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

62 DEEP BRAIN STIMULATION

63 DEEP BRAIN STIMULATION MODULATION NALOXONE OPIATES + - Dorsal Periaqueductal Gray Nucleus Raphe Magnus horn

64 ENDORPHINS Enkephalin Dynorphin b Endorphin Opioid Receptors NALOXONE

65 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

66 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

67 ENDORPHINS Enkephalin Dynorphin b Endorphin Endogenous Opioid Receptors Exogenous Morphine and other opiates

68 SIDE EFFECTS MODULATION OPIATES SYSTEMIC MORPHINE OPIATE ANALGESIA Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn GUT (CONSTIPATION)

69 OPIATE ANALGESIA MODULATION OPIATES EPIDURAL MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn

70 MORPHINE

71 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

72 S1 ACC Under Hypnosis Rainville et al HIGH Unpleasantness LOW

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