NK(1) receptor activation leads to enhancement of inhibitory neurotransmission in spinal substantia gelatinosa neurons of mouse

Substance P (SP) is a well-established pain messenger in the spinal cord, although its role in substantia gelatinosa (lamina II) still remains elusive. We carried out patch-clamp recordings on lamina II neurons from transverse mouse spinal cord slices (P8–12), using the selective NK1 receptor agonist [Sar9,Met(O2)11]-SP (SM-SP, 3–5 mM) in the presence of NBQX. Activation of NK1 receptors was confirmed after preincubation with selective NK1 antagonist L732,138 (4 mM) that consistently blocked the effects of SM-SP (nine neurons). After SM-SP challenge and spontaneous inhibitory post-synaptic current (sIPSC) analysis, 50% of recorded neurons (15 out of 30) were found to display a transient increase in frequency; in five neurons this was also associated with increase of peak amplitude. Five out of eight neurons displayed pure GABAA receptor-mediated sIPSCs, whereas the remaining ones showed mixed GABAergic/glycinergic events. After miniature IPSC analysis, a significant increase in frequency was observed in three out of 14 SM-SP responsive neurons. At least four different morphological types were apparent among NK1-responsive neurons after filling with Lucifer Yellow/biocytin: fusiform with dorso-ventral dendritic arbors (i); round-to-oval with dendritic arborization mainly directed to lamina I (ii) or III (iii), and round-to-oval with dendrites sparsely distributed all around the cell body (iv). Thus, there was no correlation between morphology and electrophysiological properties of responsive neurons. Our observations provide new insights on the processing of sensory neurotransmission in spinal cord, and indicate that activation of NK1 receptors is involved in the maintenance of the inhibitory tone of substantia gelatinosa interneurons.