Substantia gelatinosa substance

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. 

Mechanism of action Opioids exert their major effects by interacting with opioid receptors in the CNS and the gastrointestinal tract. Opioids cause hyperpolarization of nerve cells, inhibition of nerve firing, and presynaptic inhibition of transmitter release. Morphine acts at k receptors in lamina I and II of the substantia gelatinosa of the spinal cord, and decreases the release of substance P, which modulates pain perception in the spinal cord. Morphine also appears to inhibit the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli. 

Davies J, Dray A (1980) Depression and facilitation of synaptic responses in cat dorsal horn by substance P administered into substantia gelatinosa. Life Sci 27 2037-2042 Davis BJ, Smith HM (1999) Neurokinin-1 receptor immunoreactivity in the nucleus of the solitary tract in the hamster. Neuroreport 10 1003-1006... 

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