Which of the following best describes the mechanism of action of gabapentinoids (gabapentin, pregabalin) in neuropathic pain?

• A Blockade of sodium channels in peripheral nociceptors
• B Competitive antagonism at NMDA glutamate receptors in the dorsal horn
• C Inhibition of COX-2 enzyme in central sensitisation pathways
• D Binding to the α2δ subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release in spinal dorsal horn ✓

Explanation

Gabapentin and pregabalin bind to the α2δ-1 subunit of voltage-gated calcium channels in primary afferent terminals and spinal dorsal horn neurons. This reduces calcium influx, thereby decreasing the release of excitatory neurotransmitters (glutamate, substance P, CGRP) at synapses — attenuating central sensitisation and allodynia. They are first-line agents for neuropathic pain (diabetic neuropathy, post-herpetic neuralgia, fibromyalgia) and perioperative opioid-sparing. They are NOT sodium channel blockers (that is the mechanism of local anaesthetics and anticonvulsants like carbamazepine). Ketamine is the NMDA antagonist.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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