Ketamine is used as an adjunct in chronic pain management. At sub-anaesthetic doses, what is its primary analgesic mechanism?

• A Mu-opioid receptor agonism in the dorsal horn
• B Alpha-2 adrenergic agonism in the spinal cord
• C NMDA receptor antagonism — reduces central sensitisation, wind-up, and opioid-induced hyperalgesia ✓
• D COX-2 inhibition in peripheral inflamed tissues

Explanation

At sub-anaesthetic doses (0.1–0.5 mg/kg IV bolus or 0.1–0.2 mg/kg/hour infusion), ketamine's primary analgesic mechanism is non-competitive NMDA receptor antagonism in the dorsal horn of the spinal cord. NMDA receptor activation by glutamate is central to wind-up (temporal summation leading to central sensitisation). By blocking NMDA receptors, ketamine interrupts central sensitisation, reduces opioid tolerance, and reverses opioid-induced hyperalgesia (OIH). It also has modest opioid-sparing effects. These properties make it valuable in opioid-resistant cancer pain, fibromyalgia, complex regional pain syndrome, and perioperative opioid-sparing protocols.

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

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