Which statement best describes the mechanism by which duloxetine helps neuropathic pain?

• A. Inhibition of serotonin and norepinephrine reuptake, enhancing descending pain inhibition.
• B. Blockade of voltage-gated calcium channels.
• C. Sodium channel blockade in neurons.
• D. GABA receptor agonism.

Answer: (B)

Duloxetine helps neuropathic pain mainly by inhibiting the reuptake of serotonin and norepinephrine, which increases their levels in the synapse. This boosts the brain’s descending inhibitory pathways that travel down to the spinal cord, strengthening the suppression of pain signals at the dorsal horn. In neuropathic pain, this enhanced monoaminergic inhibition dampens abnormal pain signaling and reduces sensitivity.

Blockade of voltage-gated calcium channels, as seen with gabapentinoids, reduces neurotransmitter release in the spinal cord but is not how duloxetine works. Sodium channel blockade reduces neuronal excitability, a mechanism more typical of certain anticonvulsants and local anesthetics. GABA receptor agonism would broadly enhance inhibitory signaling, but duloxetine does not act primarily through GABA.