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C. Belmonte, C.L. Luna, J. Gallar; Cgrp is Released by Selective Stimulation of Polymodal Nociceptor but Not of Cold Receptor Nerve Fibers of the Cornea . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1391.
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Purpose:To study the release of the proinflammatory neuropeptide Calcitonin Gene-Related Peptide (CGRP) from corneal nerves, induced by selective stimulation of polymodal nociceptor and cold sensory nerve fibers Methods: Corneas from female OF-1 adult mice were excised under general anesthesia and sequentially placed for 5 min in 1) control saline at 25°C, 2) test solution and 3) control saline at 25°C. Test solutions were: 1) saline at 10°C; 2)saline at 5°C plus 0.1mM L-menthol; 3) capsaicin 33mM at 25°C. CGRP released into the bathing solution was measured using a commercial enzyme immunometric assay (EIA, Spibio, France). CGRP concentration was expressed in relation with the dry weight of the cornea. Results:The mean basal CGRP release was 20.52±3.05 pg/mg at 25°C (n=11). Exposure of the cornea to capsaicin 33mM increased significantly neuropeptide release (63.21± 6.12 vs. 63.21±10.57 pg/mg). Temperature decreases to 10°C reduced significantly the basal release of CGRP (14.70±0.8 vs. 5.40±3.1 pg/mg, p<0.001, n=4). A similar reduction was obtained when corneal cold sensory nerves were more strongly activated by saline at 5°C containing the selective cold nerve fiber activator L-menthol (23.77±2.37 vs. 13.97±1.45 pg/mg, p< 0.05, n=3). Conclusions:Polymodal corneal sensory nerves that are selectively excited by capsaicin release CGRP. In contrast, cold sensory fibers do not release CGRP in response to moderate or strong stimuli. The data suggest that only nerve fibers signalling pain release CGRP and contribute to the neurogenic inflammation. Innocuous cold sensory fibers do not release the neuropeptide and do not seem to participate in the inflammatory response. Supported by SAF99-0066-C02-01 and 02 from the Ministerio de Educación y Cultura. C. Luna had a fellowship from Instituto UPSA del Dolor, Madrid, Spain.
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