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PAIN!!!

DENT/OBHS 131 Neuroscience. PAIN!!!. 2009. Pain…. Is a submodality of somatosensation Is the perception of unpleasant or aversive stimulation (sensory and emotional experience) Warns of injury (physiological relevance) Is highly individual and subjective. General topics.

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PAIN!!!

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  1. DENT/OBHS 131Neuroscience PAIN!!! 2009

  2. Pain…. • Is a submodality of somatosensation • Is the perception of unpleasant or aversive stimulation (sensory and emotional experience) • Warns of injury (physiological relevance) • Is highly individual and subjective

  3. General topics • Brief review of somatosensation • Anatomical pathways • Substance P • Nociceptors • Gating theory • Descending control • Opioids / morphine • Placebo effects

  4. Learning Objectives • Describe the course of the spinothalamic (and trigeminal) tract(s) from dermatome to cortex • Describe the types of fibers carrying pain information, including their relative conduction velocities, substances they release and where they terminate in the spinal cord and periphery • Discuss how the major types of nociceptors respond to damage / injury • Know that other ascending pathways are involved in pain transmission • Discuss the descending regulation of noxious information signaling • Explain how ascending pain information is “gated” in the spinal cord

  5. Dual ascending sensory pathways • Dorsal columns / ML • Anterolateral system • Several distinct pathways • convey different aspects of pain - see later • e.g. spinothalamic - awareness and location of pain

  6. Afferents Lissauer’s tract Sub P Superficial layers of dorsal horn Ventral White Commissure (VWC) III Pain and temperature Small DRG processes enter the cord:, synapse in the substantia gelatinosa, then cross in the VWC and ascend.

  7. Learning Objective #2 • Describe the types of fibers carrying pain information, including their relative conduction velocities, substances they release and where they terminate in the spinal cord and periphery

  8. C fibers use two transmitters:substance P and glutamate • Substance P released with strong stimuli • Act to enhance and prolong the action of glutamate acting on AMPA receptors

  9. Afferent termination in dorsal horn • Many nociceptive fibers terminate in layer I (marginal layer) and II (substantia gelatinosa) of dorsal horn of spinal cord • Some pain and non-noxious sensory (e.g., proprioception) into other layers (including ventral horn - important for reflexes)

  10. Conduction velocities • Nociceptive afferents in peripheral nerve • Fast sharp pain and slow dull burning pain • myelination & axon diameter

  11. Nociceptors are free nerve endings

  12. Learning Objective #3 • Discuss how the major types of nociceptors respond to damage / injury

  13. Nociceptors • Harmful stimuli activate nociceptors • Nociceptors are peripheral free endings of primary sensory DRG and trigeminal ganglia neurons • Membrane contains receptors • Classes (all located in skin and deep tissues) • Thermal - extreme temperatures – A fibers • Mechanical - intense pressure – A fibers - sharp pain • Polymodal - intense mechanical, chemical or thermal stimuli – C fibers (unmyelinated) – dull burning

  14. Chemical nociceptors 1. Damaged cells (endothelial / platelets) - release chemicals: activate & sensitize (HYPERALGESIA) free nerve endings 2. local & central effects arachidonic acid cyclo-oxygenase (ASPIRIN) 3. vasodilation / extravasation (neurogenic inflammation)

  15. Thermal nociceptors… • …..are a separate group (interestingly including the heat-sensitive capsaicin receptor ) and are members of the transient receptor potential (TRP) gene family (non-selective cation channel) • Activated by extreme temp: • < 5 C or > 45 C • Pain & Temperature (STT) • pictured are “normal” thermoreceptors (also free nerve endings)

  16. Mechanical nociceptors…… …….are activated by very strong stimuli

  17. Sensitization of nociceptors

  18. Pain pathways sensitize!!!!! • After tissue damage, the sensation to pain to subsequent stimuli is increased at primary site of injury • Occurs in primary and secondary (surrounding) areas • Thresholds decrease or magnitude of pain from suprathreshold stimuli increases - HYPERALGESIA • Painful response to otherwise innocuous mechanical stimulus - ALLODYNIA • With severe persistent injury, C fibers fire repetitively or “wind up” resulting in increased glutamate release in spinal cord that activates NMDA receptors – synaptic plasticity

  19. Learning Objective #1 • Describe the course of the spinothalamic (and trigeminal) tract(s) from dermatome to cortex

  20. Spinothalamic • Cross • Direct to multiple thalamus

  21. Pain pathways through thalamus • VPL / VPM (neospinothalamic) • receive nociceptive specific and other sensory inputs • spinothalamic tract (STT & TTT) • project to primary somatosensory cortex • neurons have small receptive fields - injury location • Intralaminar complex (paleospinalthalamic) • receive nociceptive specific inputs • Includes projections from the spinoreticulothalamic tract • diffuse cortical projections

  22. Learning Objective #4 • Know that other ascending pathways are involved in pain transmission

  23. Ascending pain pathways • Spinoreticular tract; to reticular formation of pons / medulla (level of attention); and onto thalamus • Spinomesencephalic tract; to mesencephalic reticulum, lateral periqaueductal grey in midbrain; and on to hypothalamus and limbic system (emotion and memory integration)

  24. Spinoreticular • Collaterals - medulla • Synapses - pons • Spinoreticulothalamic tract

  25. Spinomesencephalic • Synapse - midbrain • Descending control

  26. Learning Objective #5 • Discuss the descending regulation of noxious information signaling

  27. Descending control Direct stimulation of PAG - specifically reduces sensation of pain

  28. Other transmitters Descending pathways can regulate relay of nociceptive information in the spinal cord NA (opioids) 5-HT opioids

  29. Local circuit interneurons….. • …in the spinal cord: • integration of ascending and descending information to modulate nociception • Placebo effect

  30. Learning Objective #6 • Explain how ascending pain information is “gated” in the spinal cord

  31. Gating control hypothesis of pain

  32. Cortical representation of pain • VPL / VPM project to primary somatosensory cortex and then to secondary somatosensory cortex: • Awareness, location and “intensity” of pain • Medial thalamus projects to anterior insular cortex: • Autonomic / visceral component of pain • Intralaminar nuclei of medial thalamus projects to anterior cingulate cortex (limbic association cortex): • Emotional component of pain (circuit of Papez)

  33. Referred pain Silent nociceptors: normally not active but firing threshold reduced by various insults Convergence of somatic and visceral afferents on lamina V

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