Spinal neurons exhibiting a specific nociceptive response receive abundant substance P-containing synaptic contacts.

Substance P has been implicated in nociceptive transmission in the spinal cord. However, evidence for a direct correlation between a specific nociceptive response in spinal dorsal horn neurons and substance P input is lacking. In this study, we combine intracellular recording from dorsal horn neurons in vivo, characterization of their nociceptive responses, intracellular labeling by injection of horseradish peroxidase, and immunocytochemical demonstration of substance P at the electron microscopic level. The results reveal that dorsal horn neurons that respond to noxious cutaneous stimulation with a slow, prolonged excitatory postsynaptic potential receive a preferentially high number of substance P fibers compared with nonnociceptive neurons, which scarcely receive any substance P input. Therefore, this study provides direct evidence of a structural-functional link for a substance P-mediated nociceptive response.