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Substance p in sensory nerve fibers contributes to the development of edema in the rat hind paw after thermal injury


, : Substance p in sensory nerve fibers contributes to the development of edema in the rat hind paw after thermal injury. British Journal of Pharmacology 82(1): 217-222

Immersion of the hind paws of anesthetized rats in hot water for 15 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45.degree. C, a maximal response was obtained between 55.degree. and 60.degree. C. Pretreatment of rats 2 days after birth with 50 mg kg-1 capsaicin significantly reduced the Evans blue extravasation induced by hot water at 50.degree., 55.degree. and 60.degree. C, whereas guanethidine pretreatment 24 h before the experiment caused a significantly increased response at 40.degree., 45.degree. and 50.degree. C. When Evans blue was injected between 10 and 120 min after immersion of the paw in hot water, a significant extravasation of the dye was no longer detectable. The weight of the paw as well as the weight of the piece of skin taken for Evans blue quantification increased during this period indicating the progressive development of edema in the skin and underlying tissues. In rats treated with capsaicin as neonates, the increase in paw weight after immersion in water of 50.degree. C for 5 min was significantly delayed during the 1st h, but there was no difference after 2 h. In rats pretreated with D-Arg1,D-Pro2, D-Trp7,9,Leu11-substance P, a substance P (SP) antagonist, the Evans blue extravasation was significantly reduced. The response, which remained in rats treated with capsaicin as neonates was not blocked by the SP-antagonist. Activation of peripheral branches of sensory SP neurons contributes to the initial massive protein extravasation and to the subsequent rate of development of edema following heat injury. Release of histamine did not significantly contribute to this response at the lower temperatures, although the response was reduced by histamine receptor blocking drugs at 55.degree. C and 60.degree. C. Decreasing the sympathetic vasoconstrictor tone by guanethidine resulted in an increased response.

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PMID: 6203590


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