Which neurotransmitters are first-line mediators of transmission in the superficial dorsal horn for acute nociceptive signaling?

• A. GABA and glycine
• B. Dopamine and norepinephrine
• C. Glutamate and substance P
• D. Endorphin and enkephalin

Answer: (C)

In the superficial dorsal horn, the initial transmission of acute nociceptive signals relies on fast excitatory signaling from the primary afferent fibers. Glutamate is the main fast neurotransmitter released by both A-delta and C fibers, binding to AMPA and NMDA receptors on postsynaptic neurons to generate rapid excitatory postsynaptic potentials that transmit the pain signal up to the next neurons in the pain pathway.

Substance P, a neuropeptide co-released with glutamate from the same nociceptors (especially C fibers), binds to NK1 receptors and produces a longer-lasting depolarization, enhancing excitability and contributing to central sensitization. Together, glutamate and substance P are the primary mediators driving acute nociceptive transmission in this region.

GABA and glycine are inhibitory neurotransmitters that dampen pain signaling, helping regulate transmission rather than initiating it. Dopamine and norepinephrine modulate pain through broader descending pathways and context-dependent effects rather than serving as the first-line transmitters at the dorsal-horn synapse. Endorphins and enkephalins are endogenous opioids that suppress transmission via mu receptors, not mediators of the initial excitatory signaling.