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Obsessive-Compulsive
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Pain
Schizophrenia
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Criminal Genes and The Law
 
 

 

 

Pain

cetylcholine receptor, nicotinic (nAChR) [GE]
    Mice generated lacking the alpha4 subunit and beta2 subunit of the nicotinic acetylcholine receptor. The response to painful stimuli was not any different in wild-type mice, mice lacking the alpha4 subunit, or mice lacking the beta2 subunit. However, the antinociceptive response to nicotine was reduced in both knockout strains. Results suggest that the alpha4 and beta2 subunits are components of the nicotinic pain pathways. Marubio et al., Nature, 398:805-810, 1999.

ß-arrestin-2 [GE]
    G-protein coupled heptahelical receptors (GPCR) are regulated by GPCR kinases (GRKs) which phosphorylate activated receptors and promote their interaction with ß-arrestins.  The downstream interaction of arrestins with the phosphorylated GPCR receptor inhibits further  between GPCR and guanine nucleotide binding proteins (G-proteins), dampening the signalling cascade associated with receptor activation.  This eventually leads to GPCR desensitization.  Knock-out mice deficient in ß-arrestin-2 (ßarr2-KO or ßarr2 -/-) were produced by homologous recombination.  ßarr2-KO mice displayed enhanced and prolonged morphine-induced antinocieception when compared to wild-type mice.  The response of mice to a hot-plate stimulus (56ºC) was determined before and after morphine administration.  Knock-out mice showed a significant potentiation of morphine-induced analgesia, exhibiting analgesia for up to four hours after a single dose of morphine while, in control mice, the effects wore off after only 90 minutes.  Morphine-induced analgesia is mediated by the mu-opioid receptor.  It is suggested that the deficiency in  ß-arrestin-2 improves the tolerance to pain in the presence of morphine by impairing receptor desensitization.  Bohn et al., Science, 286:2495-2498, 24 Dec. 1999.  ßarr2-KO mice, in contrast to wild-type mice, failed to become tolerant or less responsive to the antipain properties of morphine after both acute and chronic administration.  Biochemical studies showed that desensitization of the mu-opiate receptor occurred in wild-type mice, but not in ßarr2-KO mice, indicating that desensitization of the mu-opiate receptor contributes to morphine tolerance.  Bohn et al., Nature, 408:720-723, 7 Dec. 2000. See, Entry under Craving, Opiate, for ß-arrestin-2.

neuropeptide Y1 receptor [GE]
    Neuropeptide Y ("NPY") has antinociceptive activity, apparently by inhibiting the release of substance P and other "pain neurotransmitters" in the spinal cord dorsal horn.  Mice deficient in the neuropeptide Y1 receptor were created by homologous recombination.  These mice showed increased sensitivity to thermal, chemical, and mechanical pain.  The results suggest that Y1 ligand may mediate antinociception.  Naveilhan et al., Nature, 409:513-517, 25 Jan. 2001.

preprotachykinin (PPY-A); neurokinin A (NKA); substance P [GE]
    Transgenic "knock-out" mice were produced for the PPY-A gene which codes for NKA and substance P. Response to mildly painful stimuli was intact and similar to wild-type mice but the response to moderate to intense stimuli was significantly reduced. Results suggest that tachykinins cause release of tachykinins which are critical neurotransmitters for moderate and intense pain messages. Cao et al., Nature, 392: 390-394, 1998; Zimmer et al, Proc. Natl. Acad. Sci., 95:2630-2635, 1998.