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A. Matynia, S. Parikh, B. Chen, S. Nusinowitz, M. B. Gorin; Behavioral and Pharmacological Analysis of Light Associated Allodynia. Invest. Ophthalmol. Vis. Sci. 2010;51(13):675.
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Light-associated allodynia (LAA), frequently referred to as photophobia, is not a fear of light as suggested by the common descriptive term, but is the perception of discomfort or pain in the presence of normal levels of light. Numerous conditions, from corneal abrasions to genetic disorders such as cone dystrophy and achromatopsia, result in LAA, however, the mechanisms underlying LAA are unknown. These studies examine the peripheral light detection pathways that mediate LAA.
We use a light avoidance behavioral assay using analgesics and anxiolytics to determine light avoidance behavior separately from anxiety-related behavior in mouse genetic mutants that selectively disrupt one or more components of light detectiion pathways.
Functional cone or rod photoreceptors are not required for LAA as mutant strains in which cone (GNAT2, n=6) or rod alpha-transducin (GNAT1, n=10),cyclic nucleotide gated channel subunit alpha3 (CNGA3, n=7) or retinal pigment epithelial G-protein coupled receptor (RGR, n=6) (which encodes a light sensor expressed in the retinal epithelium) are deleted show no altered light avoidance behavior compared to wild type controls. Anxiolytic (2 mg/kg buspirone, n=11) and analgesic (5 mg/kg carprofen, n=13; 15mg/kg imipramine, n=13) drugs did not significantly affect light avoidance behavior in C57Bl6J mice. In contrast, the classic analgesic morphine greatly enhances LAA in C57Bl6 mice (n=26), and is reversed by naloxone (n=13). Morphine is known to act centrally but may also mediate this effect peripherally as b-waves are enhanced in electroretinograms after systemic administration of morphine (Vmax = 742 +/- 33, n=6) compared to saline (Vmax = 577+/- 39, n=6) in C57Bl6J mice.
We have determined that neither rod nor cone photoreceptors, nor RGR-opsin are required for LAA behavior: it is possible that other opsins such as melanopsin or a combination of photodetectors, for example both rods and cone photoreceptors, are required. Systemic administration of low-dose morphine is a novel atraumatic acute murine model of severe LAA that will facilitate future studies of the neural and biological basis of this clinically significant pathologic process.
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