NEW Added to close a syllabus gap — management of chronic pain is its own top-level syllabus section with three sub-items.

Pain

The pathway from nociceptor to cortex, how it is modulated, and the management of acute, chronic and cancer pain.

The pain pathway

Stage	What happens
Transduction	Noxious stimulus → nociceptor. Mediators: bradykinin, prostaglandins, substance P, histamine, H⁺, K⁺ (the "inflammatory soup"). NSAIDs and LAs act here
Transmission	A-delta — thinly myelinated, fast (5–30 m/s), sharp first pain. C fibres — unmyelinated, slow (<2 m/s), dull second pain
Modulation	Dorsal horn of the spinal cord (Rexed laminae I, II and V). Opioids, ketamine, α₂ agonists and LAs act here
Perception	Second-order neurones cross and ascend in the spinothalamic tract → thalamus → somatosensory cortex. General anaesthetics act here

Gate control theory: activity in large A-beta fibres (touch, vibration) excites an inhibitory interneurone in the substantia gelatinosa, closing the "gate" to C and A-delta input. This is why rubbing an injury helps, and the basis of TENS.
Descending inhibition: periaqueductal grey → nucleus raphe magnus → dorsal horn, using serotonin, noradrenaline and endogenous opioids. This is why amitriptyline and duloxetine work in neuropathic pain.
Wind-up: repeated C-fibre stimulation causes progressively larger dorsal horn responses via NMDA receptors — the rationale for ketamine and for pre-emptive analgesia.

Term	Meaning
Allodynia	Pain from a stimulus that is not normally painful (e.g. light touch)
Hyperalgesia	Exaggerated pain from a normally painful stimulus
Hyperpathia	Delayed, explosive pain after repeated stimulation
Dysaesthesia	An unpleasant abnormal sensation, spontaneous or evoked
Neuropathic pain	Pain caused by a lesion or disease of the somatosensory system
Chronic pain	Pain persisting beyond 3 months, or beyond normal tissue healing

Step 1 — non-opioid: paracetamol, NSAID. Step 2 — weak opioid: codeine, tramadol. Step 3 — strong opioid: morphine, oxycodone.
Adjuvants at every step: antidepressants, anticonvulsants, steroids, bisphosphonates.
Designed for cancer pain and ascended as needed; in acute pain it is used in reverse, descending as pain settles.

Multimodal analgesia — combining agents with different mechanisms gives better relief with fewer opioid side effects.
PCA — typical morphine bolus 1 mg with a 5-minute lockout, no background infusion in the opioid-naive. Requires monitoring for sedation and respiratory rate.
Regional techniques — epidural, paravertebral, peripheral blocks, catheters.
Adjuncts: ketamine, clonidine, magnesium, lidocaine infusion, gabapentinoids.

First line: amitriptyline, duloxetine, gabapentin or pregabalin. Gabapentinoids act at the α₂δ subunit of voltage-gated calcium channels — despite the name, gabapentin has no action at GABA receptors.
Topical lidocaine or capsaicin for localised pain. Conventional opioids are relatively ineffective.
Multidisciplinary care is the standard: medical, physiotherapy, psychology. Cognitive behavioural therapy and pain management programmes address the psychological dimension — catastrophising, fear-avoidance, and deconditioning.
Interventional options: nerve blocks, radiofrequency denervation, epidural steroid, spinal cord stimulation, intrathecal pumps.

Coeliac plexus block for pancreatic and upper abdominal visceral pain; splanchnic nerve block as an alternative. Superior hypogastric block is for pelvic pain — a common distractor.
Regular background analgesia plus breakthrough dosing; typical breakthrough dose is one sixth of the 24-hour total.
Manage the accompanying symptoms: nausea, constipation (always co-prescribe a laxative), breathlessness, and agitation.
Total pain — Cicely Saunders' concept that physical, psychological, social and spiritual distress all contribute and must all be addressed.