What is the current first-line treatment for neuropathic pain?

• A. Gabapentin
• B. Duloxetine
• C. Pregabalin
• D. Amitriptyline

Answer: (A)

Neuropathic pain often responds best to drugs that dampen abnormal nerve signaling, and a gabapentinoid is a common starting choice because it has strong supporting evidence across several neuropathic pain conditions and a tolerable safety profile. Gabapentin works by binding to the alpha-2-delta subunit of voltage-gated calcium channels in the dorsal horn, which reduces calcium entry and the release of excitatory neurotransmitters. That decrease in excitatory signaling lowers the hyperexcitability of damaged nerves that drives neuropathic pain.

Dosing is typically titrated up to an effective level, with careful adjustment for kidney function since it’s renally cleared. Common side effects include dizziness and drowsiness, especially early on, which often diminish as treatment continues.

Other first-line options, like duloxetine and pregabalin, are also effective and may be chosen based on individual tolerance and comorbidities, while amitriptyline can be limited by anticholinergic effects and cardiac risks—factors that sometimes make gabapentin a preferred starting agent.