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Mechanism Of γ-aminobutyric Acid Inhibiting Noxious Information Transmission And The Modulatory Effects Of Methionine-enkephalin On It In The Rat Spinal And Medullary Dorsal Horns

Posted on:2004-04-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:H LiFull Text:PDF
GTID:1104360092491711Subject:Human Anatomy and Embryology
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The superficial laminae (laminae I and II) of the spinal dorsal horn, especially lamina II (substantia gelatinosa, SG) which is composed mainly of small interneurons, receive primary afferent C fibers which transmit peripheral noxious information, and descending projection fibers from central endogenous antinociceptive system. The medullary dorsal horn (also called spinal trigeminal nucleus caudalis), the morphological and functional equivalent of the spinal dorsal horn, plays important roles in processing and regulating effects on oro-facial noxious information transmission.y-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. GABA acts as neurotransmitter in about 50% central synaptic regions, it plays important roles in modulating the excitability of neurons via binding to its specific receptors. There are three types of GABA receptors: GABAA, GABAB and GABAC receptors. GABAA and GABAC receptors belong to ligand-gated Cl- channels, while GABAB receptor belongs to G protein-coupled receptor. Immunohistochemical studies have shown that GABA-like immunoreactive (GABA-LI) neurons, fibers, terminals and GABAA and GABAB receptors are intensely located in the superficial laminae of the spinal and medullary dorsal horns. GABAc receptor locates mainly in the retina, does notdistribute in the spinal cord and medullary oblongala.Several lines of evidence suggest that GABA plays important functions in the processes of the transmission and modulation of nociceptive information in the spinal and medullary dorsal horns. In the spinal and medullary dorsal horns, GABA has been confirmed to inhibit the transmission of the peripheral nociceptive information via inhibiting the release of glutamic acid (Glu) and substance P (SP) from primary afferent fibers (pre-synaptic machanism). But the studies, especially the morphological studies, about the post-synaptic mechanisms of GABA modulating the transmission of nociceptive information in the spinal and medullary dorsal horns are still insufficient, need to be further improved and consummated.Previous morphological and physiological studies have suggested that nociceptive information being carried by primary afferent Glu- or SP-containing fibers might be relayed directly onto GABA-containing neurons, these inhibitory interneurons, in turn, might suppress the activities of the excitatory projection neurons and interneurons to participate in the modulation of noxious information transmission in the spinal and medullary dorsal horns. But the morphological evidence of GABA directly inhibiting the neurons that receive the peripheral nociceptive information in the superficial laminae of spinal and medullary dorsal horns are still deficient.Previous physiological studies have suggested that serotonin (5-HT) and noradrenaline (NE) released from the central endogenous antinociceptive system first activate GABAergic and/or glycinergic interneurons, then GABA and/or glycine released from GABA- and/or glycine-containing neurons exert inhibitory effects on excitatory projecting neurons and interneurons in the medullary and spinal dorsal horns. This supposition is still deficient of morphological evidence.By using whole-cell patch-clamp recording technique, our previous studies have demonstrated that: ① GABA acts on GABAA receptors and elicits inward Cl- currents (IGABA) in the superficial laminae of the spinal dorsal horn; ② 5-HT or NE alone can not induce noticeable currents in the superficial laminae of the spinal dorsal horn, but 5-HT or NE can potentiate GABA-induced currents by activating 5-HT2-receptor or α2 receptor via intracellular protein kinase C (PKC) or protein kinase A (PKA) signal transduction pathway. But the studies on the modulatory effects ofopioid peptides, such as enkephalin most of which are co-existed with GABA, on GABA-induced currents in the superficial laminae of spinal dorsal horn are still insufficient.According to these hints, the present study was principally designed to investigate th...
Keywords/Search Tags:spinal dorsal horn, medullary dorsal horn, nociceptive information, γ-aminobutyric acid, 5-hydroxytryptamine (serotonin), substance P, calcium binding proteins, FOS, methionine-enkaphalin, opioid receptor, immunohistochemistry
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