The role of substance P and calcitonin gene-related peptide in neurogenic plasma extravasation and vasodilatation in the rat.

Immunohistochemistry combined with retrograde tracing has been used to show that of the afferent neurons supplying the dorsomedial surface of the hind paw, approximately 30% contain substance P and 50% calcitonin gene-related peptide immunoreactivity. Stimulation of the saphenous nerve causes plasma extravasation and antidromic vasodilatation in this area of skin. The roles of calcitonin gene-related peptide and substance P released from peripheral afferent endings in mediating these effects were examined using immunoneutralization. In pilot experiments, the binding of radiolabelled peptide to the immunoglobulin fraction of calcitonin gene-related peptide and substance P antisera was characterized in quasi-physiological conditions. Systemic administration of either substance P or calcitonin gene-related peptide antibodies caused a significant decrease (P less than 0.05) in plasma extravasation measured by the Evans Blue method in response to topical application of mustard oil (0.5%) to the skin, or of capsaicin (5 microM) to the saphenous nerve. Topical application of mustard oil also produced a 52.9 +/- 5.1% increase in skin red cell flux. This increase was significantly decreased by both substance P and calcitonin gene-related peptide antibodies. The results suggest that both peptides are involved in mediating neurogenic inflammatory responses.