Synaptic Connections Of The Neurokinin 1 Receptor-like Immunoreactive Neurons In The Medullary Dorsal Horn Of The Rat

The medullary dorsal horn (MDH) receive inputs from small-diameter thin-myelinated Aδand unmyelinated C fibers. Within the superficial laminae (laminaeⅠandⅡ) of the MDH, the primary afferent inputs terminate onto projection neurons and interneurons that send their axons outside and within the nucleus, respectively, to participate in the integration and transmission of nociceptive information from orofacial region to higher brain centers.The initial integrative processing of nociceptive information in spinal dorsal horns involves inhibitory local circuits, in whichγ-aminobutyric acid (GABA) and glycine (Gly) play fundamental roles as neurotransmitters. In addition, the superficial laminae of the dorsal horn receive dense descending inputs, including serotoninergic and norepinephrinergic systems. SP is a kind of classic excitatory neurotransmitter in spinal dorsal horn. Its receptors divide into three groups: NK1R, NK2R and NK3R. NK1R is the most sensitive receptor with SP. In the spinal and medullary dorsal horns, neurokinin 1 receptor (NK1R) (SP receptor)-like immunoreactivities have been found principally in laminaeⅠandⅢ, from which the major pathways relaying noxious information to the thalamus, namely the spinothalamic tract and trigeminothalamic tract, are originated.The MDH is cytoarchitecturally and functionally similar to that of the spinal dorsal horn, and the results of functional studies have revealed that GABA, Gly, 5-HT and NE are mainly involved in the antinociceptive effects. NK1R -like immunoreactive (LI) neurons play an important role in transmitting nociceptive information. Studying the relationship between NK1R - LI neuron and inhibitory neurotranmitters plays an important role in elucidating the transmittion of orofacial pain. However, there has been little evidence on the connections between them. Therefore, the present study was performed to elucidate the relationship under electron microscope by using a pre-embedding immunohistochemical double-staining technique for GABA-, Gly-, 5-HT- or NE-containing terminals and NK1R - LI neurons in the MDH. We found that some of these GABA-, Gly-, 5-HT-, or DBH-LI axon terminals were observed to make principally symmetric synapses with NK1R -LI neuronal cell bodies and dendritic processes in laminaeⅠ,ⅡandⅢof the MDH. The present results suggest that neurons expressing NK1R within the MDH might be modulated by GABAergic and glycinergic inhibitory intrinsic neurons located in the MDH and 5-HT- or norepinephrine (NE)-containing descending fibers originated from structures in the brainstem. Our results play an important significance in revealing the inhibitory intrinsic circuit in the MDH. It provides basic evidence for elucidating the mechanism of transmitting and modulation of pain.