1. Pain is subjective Self-experience Experience depends on circumstances Pain can cause many different reactions: –Activate autonomic system (heart rate, blood pressure, sweating, etc.) –Muscle activity –Mood (fear, anxiety, depression) –Prevent sleep

2. Pain occurs with different degrees of severity Mild pain: Does not interfere noticeably with everyday life Moderate pain: May cause some annoyance and perceived as unpleasant Severe chronic pain: Affects a person’s entire life in major ways

3. There are many forms of pain Mild pain: Does not interfere noticeably with everyday life Moderate pain: May cause some annoyance and may be perceived as unpleasant Severe pain: Affects a person’s entire life in major ways

4. Different forms of pain Acute pain Chronic pain Somatic pain Neuropathic pain Central neuropathic pain

5. Pain has many different forms, but the same name Tinnitus has many different forms but the same name

6. There are different types of pain Somatic and visceral pain (Stimulation of nociceptors) – Pain ceases when stimulation ceases Neuropathic pain – Pain is related to the nervous system Central neuropathic pain – Plastic changes in the function of the CNS – May be persistent

7. It is important to have different names for for different disorders We cannot think about matters that do not have names The same words is used to describe very different forms of tinnitus and pain Using the same names for fundamentally different disorders is a disadvantage in studying and treating such disorders

8. Severe pain affects a person’s entire life in major ways Prevent or disturb sleep Interfere with or prevents intellectual work May cause suicide May involve limbic structures causing affective reactions Often accompanied by abnormal sensations from touch

9. How prevalent is severe pain? Some pain was reported by 86% of individuals above the age of 65 (Iowa study, 1994) The prevalence of severe pain was 33% for people at age 77 and above (Swedish study, 1996)

10. How prevalent is severe pain? Some pain was reported by 86% of individuals above the age of 65 (Iowa study, 1994) The prevalence of severe pain was 33% for people at age 77 and above (Swedish study, 1996)

11. Pain “The only tolerable pain is someone else’s pain” René Leriche, French surgeon, 1879–1955

12. There are different types of pain Somatic and visceral pain (Stimulation of nociceptors) –Pain ceases when stimulation ceases Neuropathic pain –Pain is related to the nervous system Central neuropathic pain –Plastic changes in the function of the CNS –May be persistent

14. Central neuropathic pain: –Pain sensation caused by abnormal neural activity in the CNS Hyperacusis: –Sounds are perceived louder than normal Allodynia: –Sensation of pain from normally innocuous stimulation (such as light touch) Hyperpathia: –Exaggerated and prolonged reactions to painful stimuli

15. Somatic and visceral pain (Stimulation of nociceptors) Burning (temperature) Injury Inflammation Chemicals Compression of spinal nerve roots (nervi nervorum)

16. Muscle pain

17. Relationship between commonly used terms to characterize muscle tension: Tone, stiffness, contracture, and spasm

18. Tension type headaches with trigger zones in the temporalis muscle ( ), in suboccipital, sternocleidomastoid and upper trapezius muscles (  ), from where pain attacks can be elicited

19. Neuropathic pain Pain of the nervous system Neuralgias Anesthesia dolorosa Root pain Stroke pain

20. Neuropathic pain All pain of neural origin The term is mostly used by neurologists for pain caused by disorders of peripheral nerves and cranial nerves

22. Central neuropathic pain Plastic changes in the function of the CNS (WDR neurons, thalamus)

23. Acute pain may promote development of central neuropathic pain Central neuropathic pain is a neurologic disorder

24. Acute pain sensation may not be a sign of pathology Pain sensation can be elicited by: Stimulation of nociceptors Overstimulation of other receptors

25. Acute pain has two phases: A fast (sharp) and a slow (burning) sensation The slow and delayed pain is mediated by unmyelinated fibers (C-fibers). The fast phase is mediated by myelinated fibers (A  ).

28. Fast and slow pain are different Fast pain (stinging): –Well defined with regards to location –Its strength is defined Slow pain (aching): –Diffuse, poorly localized anatomically –Difficult the estimate its strength

29. Different types of nerve fibers carry different kinds of pain

30. Temperature There are four different temperature receptors: Cool and warmth (sensory receptors) Cold and heat (nociceptors)

31. Temperature 1.Cool and warmth receptors mediate sensation of temperature 2.Cold and heat receptors are nociceptors that mediate sensation of pain. 3.Cool and warmth receptors are innervated by small myelinated (A  fibers, diameter 1-5  m, conduction velocity 5-30 m/sec). 4.Cold and heat receptor are innervated by unmyelinated fibers (C-fibers, diameter 0.2-2  m; conduction velocity 0.5-1 m/sec).

37. Wide dynamic range neuron

38. THE ANTERIOR LATERAL SYSTEM MEDIATES PAIN SENSATIONS The spinothalamic tract is the best known of the anteriorlateral tracts

39. Spinothalamic tract

42. Ascending projections of the anterior portion of the STT from neurons in lamina IV-V of the spinal horn. VPI: Ventral posterior inferior (nuclei of thalamus); VPL: Ventral posterior lateral (nuclei of thalamus); SI: Primary somatosensory cortex; SII: secondary somatosensory cortex

43. Projections of the lateral portion of the STT from cells in lamina I of the dorsal horn

44. Projection of unmyelinated C fibers. Notice: Projection to SII is bilateral but only the SI receives input from C fibers

45. Spinoreticular tract

46. Spinomesencephalic tract

47. Pathways involved in mediating the sensation of nociceptor pain

48. Input to the periaquaductal gray (PAG) and pathways that modulate transmission of pain signals by the PAG through the rostral ventromedial medulla (RVM) pathway.

49. Dorsolateral pontomesencephalic tegmentum pathway (DLTP).

50. Descending pathways from raphe nucleus (NA-serotonin pathway)

51. Innervation by the vagus nerve of organs in the lower abdomen involving the nucleus of the solitary tract (NST)

52. DLF: Dorsolateral funiculus VLF: Ventrolateral funiculus RVM: Rostroventral medulla

53. Visceral pain is different from somatic pain Inconsistent sensations Sometimes referred pain to body surface Often inescapable

54. Visceral afferent innervation in the lower body and motor (efferent) innervation.

55. Two-way connections between PAG, DLPT and RVM and their connections to the dorsal horn

56. The dual input to dorsal horn cells from RVM

57. Spinothalamic tract activate dorsomedial thalamus

58. Hypothesis about expansion of receptive field and creation of trigger points by unmasking of dormant synapses

59. Mean EMG amplitudes recorded from a muscle at a trigger point and at an adjacent non-tender muscle

60. Itch The basis of itching is poorly understood but it has similarities with pain.

61. CENTRAL NEUROPATHIC PAIN MAY INVOLVE THE SYMPATHETIC NERVOUS SYSTEM REFLEX SYMPATHETIC DYSTROPHY, RSD

62. Role of sympathetic nervous system in neuropathic pain 1.Sympathetic system is activated by stimulation of pain fibers 2.Sympathetic fibers secrete nor-epinephrine near mechanoreceptors 3.Sensitivity of mechanoreceptors increases 4.Activation of sympathetic system increases 5.Result: A viscous circle that causes RSD

64. Trauma cause activation of pain fibers (C-fibers), which sensitize WDR neurons Sensitized WDR neurons cause pressure to activate pain circuits (allodynia) Mechanoreceptors are activated by epinephrine that is secreted from sympathetic nerves in absence of mechanical stimulation

65. Contemporary hypotheses of neural mechanisms involved in generating CRPS I and II following trauma CRPS: Complex regional pain syndrome

66. Neuropathic pain Pain of the nervous system Neuralgias Anesthesia dolorosa Root pain Stroke pain

67. Central neuropathic pain Plastic changes in the function of the CNS (WDR neurons, thalamus)

68. Central neuropathic pain All pain of neural origin The term is mostly used for pain caused by disorders of peripheral nerves and cranial nerves

69. Central neuropathic pain may be caused by: Chronic inflammation Sensitization of skin receptors Changes in the connectivity of the CNS (through neural plasticity)

70. Acute pain may promote development of central neuropathic pain Central neuropathic pain is a neurologic disorder

71. Wide dynamic range neurons

72. Central neuropathic pain may develop from peripheral nerve injuries The pain is referred to the peripheral location Treatment of that location will not help The patient and the surgeon are both frustrated

73. Central neuropathic pain may involve changes in function Normally innocuous stimulation becomes painful (allodynia) Stimuli that normally cause mild pain cause an exaggerated reaction (hyperpathia)

74. Central neuropathic pain is often accompanied by altered perception of touch and pain stimuli Touch may cause pain (allodynia) Increased sensitivity to pain (hyperalgesia) Painful stimulation may cause exaggerated reaction to pain and prolonged pain (hyperpathia)

75. Central neuropathic pain may involve changes in function Normally innocuous stimulation becomes painful (allodynia) Stimuli that normally cause mild pain cause an exaggerated reaction (hyperpathia)

76. Allodynia: Pain from normally innocuous stimulation (of the skin) Hyperalgesia: Extreme sensitiveness to painful stimuli. Hyperpathia: Exaggerated subjective response to painful stimuli, with a continuing sensation of pain after the stimulation has ceased.

77. Neuropathic pain Normal From: Møller and Pinkerton, 1997 Pain Tingling Temporal integration

78. A B Temporal integration during development of carpal tunnel syndrome From: Møller and Pinkerton, 1997

79. Hyperalgesia from experimentally induced burns

80. Hypothesis for referred pain and sensitization of different nociceptors

81. Sensitization Peripherally: –Receptors Centrally –Increased synaptic efficacy –Expression of new neurotransmitters –Neuromodulators –Morphological re-organization

82. From: Møller: Sensory Systems, 2002 “Wind-up” –Response to second stimulus is stronger than the response to the first one Change in temporal integration Other phenomena associated with chronic pain

83. "Wind-up" is NMDA mediated. Response with and without an NMDA antagonist.

84. Severe neuropathic pain affects a person’s entire life in major ways Prevent or disturb sleep Interfere with or prevent Intellectual work Involve limbic structures causing affective reactions

85. How do we explain these symptoms and signs physiologically and anatomically? Where is the neural activity that give a sensation of pain generated?

86. The anatomical location of the abnormality that cause pain may be different from that to which the pain is referred Referred pain Central neuropathic pain

87. The abnormal neural activity that causes symptoms are not generated at the location where the symptoms are felt Example: Posttraumatic central neuropathic pain Phantom pain

88. Central pain pathways for pain PROJECT TO PRIMARY CORTICES WITH SPATIAL INFORMATION (“WHERE”) PROJECT OBJECTIVE INFORMATION (“WHAT”) TO MANY DIFFERENT PARTS OF THE CNS. NON-CLASSICAL PATHWAYS ALSO CONTRIBUTES TO AROUSAL

89. SUMMARY OF PATHWAYS INVOLVED IN MEDIATING THE SENSATION OF PAIN CENTRAL PAIN PATHWAYS PROJECT TO PRIMARY CORTICES WITH SPATIAL INFORMATION (“WHERE”) OBJECTIVE INFORMATION (“WHAT”) TO MANY DIFFERENT PARTS OF THE CNS (FOR EXAMPLE THE AMYGDALA) NON-CLASSICAL INFORMATION ALSO CONTRIBUTES TO AROUSAL From: Møller: Sensory Systems, 2003

90. Reversal of neural plasticity “TENS” (transderm electric nerve stimulation) has been used for many years in treatment of chronic pain Recently, sound stimulation in various forms have been introduced in treatment of severe tinnitus

91. Severe neuropathic pain affects a person’s entire life in major ways Prevent or disturb sleep Interfere with or prevent Intellectual work Involve limbic structures causing affective reactions

92. How can pain information reach the amygdala? Through the thalamus Through routes that are enhanced by expression of neural plasticity (re-routing of information)

93. From: Møller: Sensory Systems, 2003 Connections from a sensory system to the amygdala “the high route”

94. Connections from a sensory system to the amygdala “the low route” From: Møller: Sensory Systems, 2003

95. The amygdala is involved in fear and other mood disorders

96. From: Møller: Sensory Systems, 2003 Connections from the amygdala

97. INESCAPABLE PAIN INVOLVES OTHER PARTS OF THE CNS THAN ESCAPABLE PAIN Activate different columns in the PAG coordinating either active of passive coping