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) for 5 min induced temperature-dependent plasma protein extravasation at 46 degrees C to 50 degrees 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 degrees C and by up to 53 +/- 10% (120 nmol kg-1) after heat application at 50 degrees 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 degrees C. At a dose of 200 nmol kg-1 CGRP8-37 inhibited plasma extravasation by 41 +/- 8% after heat application at 50 degrees 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 degrees 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.