Pain Medicine: Mechanisms and Multimodal Logic
What you must understand
Frame pain as nociception → transmission → modulation → perception, then map drugs to each step. Know: peripheral sensitisation (bradykinin, prostaglandins, substance P), central sensitisation and wind-up (NMDA receptor involvement), and descending inhibitory pathways (opioid, noradrenergic, serotonergic). For pharmacology, understand opioid receptor subtypes (mu, kappa, delta) and their effects, the rationale for multimodal analgesia, and the distinct roles of NSAIDs, paracetamol, gabapentinoids, ketamine, and local anaesthetics. Neuropathic pain has different logic (ectopic firing, central sensitisation) and responds to gabapentinoids, tricyclics, and SNRIs rather than simple NSAIDs.
Traps in questions
- Conflating tolerance (need more drug for same effect), physical dependence (withdrawal), and addiction (compulsive use despite harm).
- Assuming opioids have a ceiling effect - they largely do not, unlike NSAIDs/paracetamol.
- Forgetting opioid-induced hyperalgesia can mimic worsening pain.
- Missing that NSAIDs act via COX inhibition and carry renal, GI, and platelet risks.
Worked rule of thumb
Use the multimodal rule: reduce each drug's dose by combining agents acting at different sites. Example: post-op pain - paracetamol (central), NSAID (peripheral prostaglandins), local anaesthetic block (transmission), opioid (central mu), ± ketamine (NMDA, central sensitisation). Each targets a distinct node, lowering total opioid requirement and side effects.