Preferential Synaptic Relationships between Substance P-Immunoreactive Boutons and Neurokinin 1 Receptor Sites in the Rat Spinal Cord

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (26), p.15775-15780
• Main Authors: McLeod, A. L., Krause, J. E., Cuello, A. C., A. Ribeiro-Da-Silva
• Format: Article
• Language: English
• Subjects: Afferent Pathways; Animals; Antibodies; Apposition; Axons - physiology; Axons - ultrastructure; Biological Sciences; Dendrites; Dendrites - physiology; Dendrites - ultrastructure; Immunohistochemistry; Innervation; Male; Microscopy; Microscopy, Electron; Models, Neurological; Neurobiology; Neurology; Neurons; Neurons - cytology; Neurons - physiology; Rats; Rats, Wistar; Receptors; Receptors, Neurokinin-1 - analysis; Receptors, Neurokinin-1 - physiology; Rodents; Spinal cord; Spinal Cord - cytology; Spinal Cord - physiology; Substance P - analysis; Substance P - physiology; Synapses; Synapses - physiology; Synapses - ultrastructure; Thalamus - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.26.15775

Substance P plays an important role in the transmission of pain-related information in the dorsal horn of the spinal cord. Recent immunocytochemical studies have shown a mismatch between the distribution of substance P and its receptor in the superficial laminae of the dorsal horn. Because such a mismatch was not observed by using classical radioligand binding studies, we decided to investigate further the issue of the relationship between substance P and its receptor by using an antibody raised against a portion of the carboxyl terminal of the neurokinin 1 receptor and a bispecific monoclonal antibodies against substance P and the horseradish peroxidase. Light microscopy revealed a good correlation between the distributions of substance P and the neurokinin 1 receptor, both being localized with highest densities in lamina I and outer lamina II of the spinal dorsal horn. An ultrastructural double-labeling study, combining preembedding immunogold with enzyme-based immunocytochemistry, showed that most neurokinin 1 receptor immunoreactive dendrites were apposed by substance P containing boutons. A detailed quantitative analysis revealed that neurokinin 1 receptor immunoreactive dendrites received more appositions and synapses from substance P immunoreactive terminals than those not expressing the neurokinin 1 receptor. Such preferential innervation by substance P occurred in all superficial dorsal horn laminae even though neurokinin 1 receptor immunoreactive dendrites were a minority of the total number of dendritic profiles in the above laminae. These results suggest that, contrary to the belief that neuropeptides act in a diffuse manner at a considerable distance from their sites of release, substance P should act on profiles expressing the neurokinin 1 receptor at a short distance from its site of release.