## Gabapentin Mechanism in Neuropathic Pain **Key Point:** Gabapentin binds to the alpha-2-delta (α2δ) subunit of voltage-gated calcium channels, reducing calcium influx into presynaptic nerve terminals and decreasing neurotransmitter release. ### Pharmacological Action Gabapentin is a gabapentinoid that: - Crosses the blood-brain barrier via the large neutral amino acid transporter type 1 (LAT1) - Binds specifically to the α2δ-1 subunit of L-type voltage-gated calcium channels - Reduces calcium entry and subsequent release of excitatory neurotransmitters (glutamate, noradrenaline) - Does NOT directly block sodium channels or NMDA receptors ### Clinical Application **High-Yield:** Gabapentin is first-line for: - Postherpetic neuralgia (PHN) - Diabetic neuropathy - Phantom limb pain - Spinal cord injury pain **Clinical Pearl:** Pregabalin, a structural analogue, has the same mechanism but higher potency and better bioavailability, making it preferred in many settings despite higher cost. ### Dosing Considerations - Requires renal dose adjustment (creatinine clearance-dependent) - Typical pain dose: 900–3600 mg/day in divided doses - Onset: 2–4 weeks for full analgesic effect [cite:Harrison 21e Ch 375] 
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