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 CGRP(1)-receptor antagonist, CGRP(8-37), 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) CGRP(8-37) inhibited plasma extravasation by 41 +/- 8% after heat application at 50 degrees C. 5 SR140333, 120 nmol kg(-1), and CGRP(8-37), 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, CGRP(8-37), 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.