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Involvement of sensory neuropeptides in the development of plasma extravasation in rat dorsal skin following thermal injury

1 The involvement of the neuropeptides, substance P (SP) and calcitonin gene‐related peptide (CGRP) in plasma extravasation following thermal injury of rat dorsal skin was investigated. 2 Heat applied to the dorsal skin of anaesthetized rats by a temperature‐controlled skin heater (1 cm diameter) fo...

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Published in:British journal of pharmacology 1996-03, Vol.117 (6), p.1065-1070
Main Authors: Siney, L., Brain, S.D.
Format: Article
Language:English
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Summary:1 The involvement of the neuropeptides, substance P (SP) and calcitonin gene‐related peptide (CGRP) in plasma extravasation following thermal injury of rat dorsal skin was investigated. 2 Heat applied to the dorsal skin of anaesthetized rats by a temperature‐controlled skin heater (1 cm diameter) for 5 min induced temperature‐dependent plasma protein extravasation at 46°C to 50°C measured over the 20 min following initiation of heat. 3 The NK1‐receptor antagonist, SR140333, at doses above 36 nmol kg−1, significantly (P < 0.05) inhibited plasma extravasation by up to 79 ± 3% (120 nmol kg−1) after heat application at 48°C and by up to 53 ± 10% (120 nmol kg−1) after heat application at 50°C. 4 The CGRP1‐receptor antagonist, CGRP8–37, at doses of 200 and 400 nmol kg−1, significantly inhibited (P < 0.01) plasma extravasation by 55 ± 9 and 60 ± 12%, respectively, after heat application at 48°C. At a dose of 200 nmol kg−1 CGRP8–37 inhibited plasma extravasation by 41 ± 8% after heat application at 50°C. 5 SR140333, 120 nmol kg−1, and CGRP8–37, 200 nmol kg−1 together significantly (P < 0.01) inhibited plasma extravasation by 84 ± 15% after heating at 48°C for 5 min. 6 In experiments where the response was measured for 0–5, 5–10, 10–15 or 15–20 min, SR140333, 120 nmol kg−1, significantly (P < 0.05) inhibited plasma extravasation which had accumulated during all the time periods measured. In comparison, CGRP8–37, 200 nmol kg−1, was significantly (P < 0.05) effective at time‐points up to 15 min after initiation of injury. 7 In longer term experiments plasma protein extravasation continued for at least 95 min after initiation of thermal injury. SR140333, at a dose of 120 nmol kg−1, significantly inhibited plasma extravasation for up to 65 min after initiation of injury. 8 In conclusion, the data from the present study demonstrate that both SP and CGRP are likely to have a role in the acute plasma extravasation after thermal injury. In addition, evidence suggests SP may have a role in plasma extravasation for up to 65 min.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1996.tb16698.x