Immunoreactive substance P release from skin nerves in the rat by noxious thermal stimulation

We have examined by radioimmunoassay the substance P (IR-SP) content of superfusate obtained from skin blisters in the anesthetized rat. The blisters were produced on the footpad using a vacuum pump, and the blister base was superfused with tyrode solution. Continuous release of IR-SP was approximately 100 pg/h from the innervated footpad but was considerably reduced when the footpad had been surgically denervated 10-14 days previously. The IR-SP content was markedly increased in the innervated footpad following a local noxious heat stimulus of 50 degrees C applied for 30 s at 5-min intervals for 1 h. The results support the proposal that SP is a mediator of neurogenic inflammation induced by noxious skin heating.