mechanism of action of analgesics (2012)
TRANSCRIPT
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Where do analgesic medications work?
Peter Kamerman
PainSA, Pretoria, South Africa, 2013
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• All four drug classes act within the CNS
• All four drug classes affect descending pain modulating pathways
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Major pain modulating pathways
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Bee & Dickenson, Future Neurol 2: 661-671, 2007
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Dorsal horn circuits
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Opioid analgesics
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Sites of mu opioid receptors
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Effect of opioids on dorsal horn circuits
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Non-opioid analgesicsParacetamol
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Sites of action of paracetamol
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Effects of paracetamol on dorsal horn circuits
Adapted from: Mallet et al., Pain 139: 190-200, 2008
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Effects of paracetamol on dorsal horn circuits
Adapted from: Andersson et al., Nat Commun 2: 551, DOI 10.1038/ncomms1559, 2011
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AntidepressantsSerotonin and noradrenaline reuptake inhibitors (SNRI)
Tricyclic antidepressants (TCA)
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Sites of action of antidepressants
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
Effects of antidepressants on dorsal horn circuits
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α2δ-antagonistsGabapentin Pregabalin
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Sites of action of α2δ-antagonists
Adapted from: McMahon & Koltzenburg: Wall and Melzack’s Textbook of Pain 5e, © Elsevier 2006
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α2δ-antagonist
↓GABA release
LC neurone
Action potential
GABAergic terminal
Calcium channel block
Adapted from: Tanabe et al., J Neurosci Res 86: 3258-3264, 2008
Effects of α2δ-antagonists on dorsal horn circuitsSUPRASPINAL MECHANISMS
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Effects of α2δ-antagonists on dorsal horn circuitsSPINAL MECHANISMS (STATE-DEPENDENT)
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Effects of α2δ-antagonists on dorsal horn circuits
Bee & Dickenson, Pain 140: 209-223, 2008
SPINAL MECHANISMS (STATE-DEPENDENT)
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Conclusion