A patient with Sjögren syndrome reports burning pain in the toes; temperature sensation is decreased but other modalities are normal. Which neurotransmitter mediates this pain?

• A. Glutamate
• B. GABA
• C. Substance P
• D. Endorphin

Answer: (C)

Pain signaling from small, unmyelinated fibers (C fibers) is what creates the burning, slow pain and is often accompanied by altered temperature sensation in small-fiber neuropathies. The key messenger released by these fibers in the dorsal horn to transmit nociceptive signals and promote sensitization is Substance P. It acts on NK1 receptors to enhance pain transmission and contribute to neurogenic inflammation, which fits the burning, persistent pain described and the loss of temperature sensation seen in small-fiber involvement like Sjögren syndrome.

Glutamate does mediate fast, sharp pain from A-delta fibers, not the dull burning quality described here. GABA is inhibitory and dampens pain signaling, and endorphins are analgesic modulators rather than primary mediators of this nociceptive transmission.