Substantia gelatinosa

Neurotensin. This hormone has been isolated and characterized from acid—acetone extracts of bovine hypothalamus (118) on the basis of its hypotensive activity. Immunoreactive neurotensin is present in mammalian gut and is distributed throughout the central nervous system its highest concentration is in the hypothalamus and in the substantia gelatinosa of the spinal cord (119). Its overall brain distribution is not unlike that of enkephalin ( ) ... 

The substantia gelatinosa is part of the dorsal horn of the spinal cord, also called lamina II . The substantia gelatinosa is made up almost exclusively of interneurons (both excitatory and inhibitory), some of which respond only to nociceptive inputs, while others respond also to non-noxious stimuli. 

Kohno T, Kumamoto E, Higashi H, Shimoji K, Yoshimura M (1999) Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol 518(Pt 3) 803-813... 

Yoshimura M, North RA (1983) Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 305(5934) 529-530... 

The mu, delta and kappa opioid receptors are coupled to G° and G proteins and the inhibitory actions of the opioids occur from the closing of calcium channels (in the case of the K receptor) and the opening of potassium channels (for /i, d and ORL-1). These actions result in either reductions in transmitter release or depression of neuronal excitability depending on the pre- or postsynaptic location of the receptors. Excitatory effects can also occur via indirect mechanisms such as disinhibition, which have been reported in the substantia gelatinosa and the hippocampus. Flere, the activation of opioid receptors on GABA neurons results in removal of GABA-mediated inhibition and so leads to facilitation. 

Lamina II is also known as the substantia gelatinosa (SG) and can be divided into two layers, the outer layer (IIo) and the inner layer (Ili). This layer is densely packed with small neurons and lacks myelinated axons. Neurons with cell bodies in Hi receive inputs from low-threshold mechanoreceptive primary afferents, while those in IIo respond to inputs from high-threshold and thermoreceptive afferents. The intrinsic cells which comprise the SG are predominantly stalk and islet cells. Stalk cells are found located in lamina IIo, particularly on the border of lamina I, and most of their axons have ramifications in lamina I although some also project to deeper layers. These cells are thought to predominantly relay excitatory transmission. Islet cells, on the other hand, are located in Hi and have been demonstrated to contain the inhibitory neurotransmitters, y-aminobutyric acid (GABA), glycine and enkephalins in their dendrites. Hence these cells have been proposed to be inhibitory interneurons. 

The cell bodies in lamina III are generally larger and less densely packed than those in the substantia gelatinosa. The main cell type of lamina III includes projection cells, which contribute to the SCT and postsynaptic dorsal column (PSDC). The dendrites of SCT cells are confined to lamina III and do not reach laminae I and IIo. However, those of PSDC are not flattened in the mediolateral plane and extend to laminae I and II, thus forming monosynaptic connections with small primary afferent fibres. 

The opiate receptors in the spinal cord are predominantly of the mu and delta type and are found in the C-fibre terminal zone (the substantia gelatinosa) in the superficial dorsal horn. Considerable numbers of ORL-1 receptors are also found in this area. Up to 75% of the opiate receptors are found presynaptically on the C-fibre terminals and when activated inhibit neurotransmitter release. The opening of potassium channels will reduce calcium flux in the terminal and so there will be a resultant decrease in... 

Yang, K., Fujita, T. 8r Kumamoto, E. (2004). Adenosine inhibits GABAergic and glycinergic transmission in adult rat substantia gelatinosa neurons. /. Neurophysiol. 92 (5), 2867-77. 

Griersmith, B. T., and Duggan, A. W. (1980) Prolonged depression of spinal transmission of nociceptive information by 5-HT administered in the substantia gelatinosa Antagonism by methysergide. Brain Res., 187 231-236. 

Melzack and Wall theorized that the transmission of a peripheral painful stimulus to the CNS occurs via a gate at spinal cord level. This gate comprises an inhibitory interneurone in the substantia gelatinosa that may be either stimulated or inhibited by different afferent inputs. A simple line diagram can be useful when explaining the mechanism to avoid confusion. 

The Ap fibres are examples of afferents that stimulate inhibitory interneurones (in the substantia gelatinosa (SG)) and, therefore, prevent nociceptive transmission to the CNS. The C fibres are examples of afferents that inhibit inhibitory interneurones and, therefore, enhance nociceptive transmission. Note that both types of fibre stimulate the second-order neurone (2°) directly but it is the intemeurone that modifies the transmission. 

Cells in the substantia gelatinosa (lamina II contains highest levels of opioid binding) of the dorsal horn of the spinal cord respond to incoming nociceptive stimuli and regulate, or gate, the transmission of nociceptive impulses to other pathways within the CNS via the... 

HT3 receptors are located exclusively on neurons and are widely distributed throughout the peripheral and central nervous systems. In the periphery, 5-HT3 receptors are found on autonomic, sensory, and enteric neurons (Fozard 1984). In the central nervous system, 5-HT3 receptors are labeled in cortex, hippocampus, caudate hypothalamus, brain stem, midbrain, and cerebellum, with the highest density in discrete nuclei of the lower brain stem (e.g., dorsal vagal complex and spinal trigeminal nucleus), the area postrema, and substantia gelatinosa at all levels of the spinal cord (Palacios et al. 1991 Waeber et al. 1989). 

On intrathecal injection, it acts on substantia gelatinosa of dorsal horn of spinal cord and inhibit the release of excitatory transmitters. At supraspinal sites, it acts on medulla, mid brain, limbic and cortical areas. 

Serotonergic and non-serotonergic fibers originating in the RVM terminate predominantly in dorsal horn laminae I, II (substantia gelatinosa), and V, which are the main targets... 

In the spinal cord, a2-agonists act on receptors located on the terminals of primary afferent fibers in the dorsal horn substantia gelatinosa to reduce nociceptive transmission by inhibiting the release of glutamate and substance P (Collin et al., 1994 Hamalainen and Pertovaara, 1995) (see Fig. 2). These receptors appear to be primarily of the a2A subtype which is negatively coupled to adenylate cyclase (Lakhlani et al., 1997 see Millan, 1999 but see Sawamura et al., 2000, and references therein for a discussion of the possible involvement of other a2-receptor subtypes in antinociception). Like activation of p-opioid receptors, the activation of a2-receptors increases the potassium conductance of the cells bearing these receptors, thus reducing cellular excitability. 

Bleazard, L., Hill, R. G., Morris, R. The correlation between the distribution of the NK1 receptor and the actions of tachykinin agonists in the dorsal horn of the rat indicates that substance P does not have a functional role on substantia gelatinosa (lamina II) neurons, J. Neurosci. 1994, 14, 7655-7664. 

Duggan, A. W., Morton, C. R., Zhao, Z. Q., Hendry, I. A. Noxious heating of the skin releases immunoreactive substance P in the substantia gelatinosa of the cat a study with antibody microprobes, Brain Res. 1987, 403, 345-349. 

Eckert WA 3rd, Light AR. Hyperpolarization of substantia gelatinosa neurons evoked by mu-, kappa-, delta 1-, and delta 2-selective opioids. J Pain. 2002 3 115-125. 

Spinal cord (substantia gelatinosa) Rat Grudt and Henderson 1998... 

Miller RJ (1998) Presynaptic receptors. Annu Rev Pharmacol Toxicol 38 201-27 Modin A, Pernow J, Lundberg JM (1994) Repeated renal and splenic sympathetic nerve stimulation in anaesthetized pigs. J Auton Nerv Syst 49 123-34 Moran TD, Colmers WF, Smith PA (2004) Opioid-like actions of neuropeptide Y in rat substantia gelatinosa Y1 suppression of inhibition and Y2 suppression of excitation. J Neurophysiol 92 3266-75... 

Xu H, Wu L-J, Zhao M-G, Toyoda H, Vadakkan K, Jia Y, Pinaud R, Zhuo M (2006) Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Molec Pain 2 29... 

Yang K, Kumamoto E, Furue H, Li Y-Q, Yoshimura M (1999) Action of capsaicin on dorsal root-evoked synaptic transmission to substantia gelatinosa neurons in adult rat spinal cord slices. Brain Res 830 268... 

Yang K, Kumamoto E, Furue H, Yoshimura M (1998) Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord. Neurosci Lett 255 135... 

Youn DH, Randic M (2004) Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit. J Physiol... 

Yue H-Y, Fujita T, Kawasaki Y, Kumamoto E (2004) AM404 enhances the spontaneous release of -glutamate in a manner sensitive to capsazepine in adult rat substantia gelatinosa neurones. Brain Res 1018 283... 

Kim HY, Kim SJ, Kim J, Oh SB, Cho H, Jung SJ (2005) Effect of nitric oxide on hyperpolarization-activated current in substantia gelatinosa neurons of rats. Biochem Biophys Res Commun 338 1648-53... 

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