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Pain Classification and Opioid Physiology

Pain Classification and Opioid Physiology. A Review. Analgesic Ladder. Non-Opioid Non-Opioid + Adjuvant Analgesic Weak Opioid Weak Opioid + Adjuvant Analgesic Strong Opioid Strong Opioid + Adjuvant Analgesic. Mechanisms of Pain. Visceral Pain Pain from abdominal & thoracic viscera

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Pain Classification and Opioid Physiology

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  1. Pain Classification and Opioid Physiology A Review

  2. Analgesic Ladder • Non-Opioid • Non-Opioid + Adjuvant Analgesic • Weak Opioid • Weak Opioid + Adjuvant Analgesic • Strong Opioid • Strong Opioid + Adjuvant Analgesic

  3. Mechanisms of Pain Visceral Pain • Pain from abdominal & thoracic viscera • Deep, squeezing, pressure. • Poorly localised. • Sometimes referred. • Liver, pancreas, lung

  4. Mechanisms of Pain Somatic Pain • ‘Nociceptive’ • Pain from nerve endings in tissues & bones • Aching, gnawing. • Well localised. • eg Bone Metastases

  5. Mechanisms of Pain Neuropathic Pain • Pain from nerve irritation/damage. • Flashing, sharp, electric, burning. • Often follows nerve pathway. • Plexus pain.

  6. Pain Pathway NA 5HT Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  7. Synapse Peripheral Nerve Spinal Nerve Synaptic Cleft

  8. Synapse Impulse Impulse Depolarisation

  9. The Busy Gate Cortico-Spinal Sympathetic Other Spinothalamic

  10. Opioid Receptors Mu - - Ca2+ - -

  11. Receptors Excitatory receptors Mu To Spino- thalamic tract K/Ca Inhibitory receptors

  12. Opioid Response Opioid level 100% % opioid receptor binding Opioid Dose

  13. Opioid Response Opioid level Side Effects 100% Maximum opioid analgesia % opioid receptor binding Opioid Dose

  14. Opioid Receptor Sites NA 5HT Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  15. Peripheral Action of Morphine Nociceptor Mu K/Ca Inflammatory cell

  16. Pain wind up

  17. Receptors and Channels AMPA Short depolarisation “Fast” Sharp, pricking pain NMDA Enhance depolarisation Greater response to stimulus Response outlasts stimulus

  18. Receptors Excitatory Receptors AMPA Mu To Spino- thalamic tract K/Ca

  19. NMDA feedback To Spino- thalamic tract K/Ca NMDA receptors NMDA receptors

  20. Receptor responses AMPA NMDA Stimulus Stimulus Impulses Impulses Time Time

  21. Receptor co-operation C-fibre response NMDA NK 1-2 AMPA Stimulus number

  22. NMDA Antagonists Very weak Paracetamol Weak Some NSAID’s Methadone Pethidine Valproate Amantidine

  23. NMDA Antagonists Moderate Ketamine Dextromethorphan Strong Experimental Lethal

  24. Opioid Response Opioid level % opioid receptor binding Opioid Dose

  25. Opioid Receptor Sites NA 5HT Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  26. Receptors Excitatory Receptors AMPA Mu To Spino- thalamic tract K/Ca

  27. Sodium Channels To Spino- thalamic tract K/Ca

  28. Receptors 1. Cell body receives electrical impulse producing Mu receptor 3. Receptors next to synapse bind opioids which stop chemical transmission of impulse To Spino- thalamic tract K/Ca 2. Mu receptors migrate down nerve cell membrane Inhibitory receptors

  29. Sodium Channel Blockers • Valproate • Gabapentin • Carbamazepine

  30. Pain Pathway NA 5HT Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  31. Paracetamol NA 5HT Paracetamol acts here Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  32. NSAID’s NA 5HT NSAIDs acts here Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  33. Morphine NA 5HT 25% Morphine acts here Cortico-Spinal Spino-thalamic Receptors 5% 70% Peripheral Nerve

  34. Dorsal Horn

  35. Dorsal Horn

  36. Neuropathic Pain • Has many mechanisms • Therefore illogical to expect one drug to work every time • Often need combination therapy

  37. Pain Pathway NA 5HT Cortico-Spinal Spino-thalamic Receptors Peripheral Nerve

  38. Opioid Receptors Mu - - Ca2+ - -

  39. Opioid Response Opioid level % opioid receptor binding Opioid Dose

  40. Side Effect Threshold High threshold Opioid level Opioid Dose

  41. Side Effect Threshold Opioid level Low threshold Opioid Dose

  42. Methadone • Potent Mu agonist • NMDA receptor activity • No active metabolites

  43. Methadone • Formulation • Oral liquid, tablets • Injection, SC, IM, IV • Not predicable • Large inter-individual variation • 1-2 hours onset, lasts 6-12 hours • t 1/2 <120 hrs, Steady state 2-10 days.

  44. Methadone • Formulation • Oral liquid, tablets • Injection, SC, IM, IV • Not predicable • Large inter-individual variation • 1-2 hours onset, lasts 6-12 hours • t 1/2 <120 hrs, Steady state 2-10 days.

  45. Side Effect Threshold Methadone side effect threshold Opioid level Morphine side effect threshold Opioid Dose

  46. Methadone Study • Retrospective • Case study - 68 patients • Morphine side effects • Co-analgesics unchanged • Opioid changed to methadone

  47. Methadone Study • Pain Types • Somatic 28 • Neuropathic 2 • Visceral 11 • SV 3 • SN 22 • SVN 1

  48. Methadone Study Side Effects • Confusion 20 • Drowsiness 34 • Hallucinations 13 • Nausea 24 • Pruritis 2

  49. Methadone Study • Case study - 68 patients • Resolution of adverse effects in 56 (82%) • Side effects same or changed in 12

  50. Morphine/Methadone Conversion Average = 6.34

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