A patient on long-term strong opioids for cancer pain develops opioid-induced hyperalgesia (OIH). The mechanism of OIH is BEST described as:

• A Tolerance to the analgesic effect due to mu receptor downregulation
• B Accumulation of toxic metabolites causing peripheral sensitisation
• C Increased prostaglandin synthesis from inhibition of spinal COX enzymes by opioids
• D Activation of NMDA receptors by glutamate, leading to central sensitisation and paradoxical pain amplification ✓

Explanation

Opioid-induced hyperalgesia (OIH) is a paradoxical state where increasing opioid doses cause increased pain sensitivity rather than analgesia. The primary mechanism involves NMDA receptor activation: chronic opioid exposure upregulates the NMDA receptor-mediated glutamate signalling pathway and facilitates central sensitisation in the dorsal horn. Dynorphin and anti-opioid peptides are also implicated. Clinically, OIH manifests as diffuse pain that is often different from the original pain and is not relieved by opioid dose escalation. Management includes opioid rotation, dose reduction, and addition of ketamine (NMDA antagonist) or clonidine. Tolerance is a distinct pharmacological phenomenon.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.