The mechanism of pregabalin as an adjunct in multimodal postoperative analgesia involves:

• A Inhibition of voltage-gated sodium channels, reducing neuronal excitability
• B NMDA receptor antagonism preventing central sensitisation
• C Enhanced GABA-A receptor chloride conductance causing central inhibition
• D Binding to alpha-2-delta subunit of voltage-gated calcium channels, reducing glutamate, noradrenaline, and substance P release ✓

Explanation

Pregabalin (and gabapentin) bind with high affinity to the alpha-2-delta (α2δ) auxiliary subunit of voltage-gated calcium channels. This reduces calcium influx at presynaptic terminals of sensitised primary afferent neurons, decreasing the release of excitatory neurotransmitters including glutamate, substance P, and noradrenaline in the dorsal horn. This anti-hyperalgesic mechanism reduces central sensitisation and opioid requirements postoperatively. Despite its structural resemblance to GABA, pregabalin does not act at GABA receptors. NMDA antagonism describes ketamine's mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.