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746 Human Brain

746 Human Brain. Pain. Pain : Aim. perception peripheral responses role of NSAIDs e.g. aspirin spinal modulation gate control peptidergic modulation CNS. Perception. pain human description

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746 Human Brain

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  1. 746 Human Brain Pain

  2. Pain : Aim • perception • peripheral responses • role of NSAIDs e.g. aspirin • spinal modulation • gate control • peptidergic modulation • CNS

  3. Perception • pain • human description • International Association for the Study of Pain: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". • phantom pain • amputees • Why do we need pain?

  4. Nocioception • noxious stimuli • animal models ? • associated with parts of CNS

  5. Peripheral responses • Specialised receptors • Pain is not just neurons firing more often • Adequate stimuli • Role of • aspirin • Paracetamol • Ibuprofen

  6. Pain is… • not just neurons firing more often

  7. Specialised receptors • Heinbecker 1933 • A-d • faster than 2.5m/s • high threshold mechanoreceptors - 20 cm-2 • sharp pain • C • slower than 1m/s • polymodal • heat - pressure - noxious chemicals

  8. Pain is… • ouch • ache

  9. Adequate stimuli • temperature • C fibers sensitive to very low concentrations of • histamine 10-8M, ACh 10-8M • Prostaglandins 10-10 M • no one chemical ?? • released by tissue damage

  10. Capsaicin • transient effect of chillies - capsaicin • Loss of nocioceptive response in new born rats with capsaicin

  11. Capsaicin • Active ingredient of chillies • Activates TRPV1 channels

  12. Role of aspirin • aspirin blocks Cyclooxygenase • = COX • = PGH synthase • covalent modification to ser - 530 • http://cti.itc.virginia.edu/~cmg/Demo/pdb/cycox/cycox.html arachidonic acid COX  prostaglandin PGG2 COX  prostaglandin PGH2

  13. Other NSAIDs • non-steroidal anti-inflammatory drugs • Ibuprofen • COX competitive inhibitor • Paracetamol • = Acetaminophen • = N-acetyl-para-aminophenol • COX-3 inhibitor

  14. Summary so far • Pain perceived • A - d and C fibres • response to pain blocked by NSAIDs • prostaglandin synthesis • Next: Spinal cord...

  15. Spinal Cord dorsal horn dorsalroot DRG ventralroot

  16. Gate control hypothesis • Melzack & Wall (1965) • in the spinal cord the pain pathway is modulated

  17. Gate control hypothesis

  18. Neuromatrix • Melzack & Wall revised their theory to elaborate on the spinal cord system as neuromatrix

  19. Evidence ? • anatomical • pharmacological • physiological • anecdotal

  20. SG substantia gelatinosa • layered • map of skin

  21. Anatomy - cont

  22. Enkaphalins in SG • drawing of nocioceptive cell in SG • enkephalin immunoreactive • enkephalin receptors mu delta kappa

  23. endogenous opioids • Tyr-Gly-Gly-Phe-Met • Tyr-Gly-Gly-Phe-Leu

  24. Morphine • derived from opium • action as analgesic in spinal cord • usually codeine OCh3

  25. Substance P • 11 amino acid peptide • Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met • Found in CNS and dorsal horn of spinal cord • Example of a tachykinin

  26. SP as a transmitter • main excitatory transmitter is glutamate • capsaicin blocks C fibers selectively

  27. tactile stimuli • Mummy rub it better ? • lateral inhibition ? • TENS

  28. Modulation in SG

  29. Summary so far: • spinal modulation • gate control or neuromatrix • tactile stimuli • TENS • SG • SP • opioids • next: CNS

  30. Gate & CNS • noradrenaline • serotonin • enkephalin • stress

  31. CNS • CNS itself not sensitive to pain • meninges are - local anaesthetic • regional specialisation • leucotomy • removal of frontal lobes / thalamus to remove pain perception PET scan shows blood flow

  32. Summary • pain as human response • peripheral control by NSAIDs • spinal control - peptide neurotransmitters • control by brain

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