Changes in the content of substance P (dorsal spinal cord, dorsal roots, dorsal root ganglia, saphenous nerve, skin) and functional changes (neurogenic plasma extravasation, chemosensitivity of the cornea) were measured in the rat from 10 min to 4 days after the s.c. injection of a single dose of 50 mg kg-1 capsaicin. 2. The substance P content in dorsal roots, saphenous nerve and hind paw skin progressively declined to about 60--70% of control 4 days after treatment, whereas that of the dorsal root ganglia rose, after an initial decline, to 140% after 1--4 days. 3. After denervation, impairment of neurogenic plasma extravasation could be observed not earlier than after one day, thus being comparable in time course to the depletion of substance P in the skin and saphenous nerve. 4. Neurogenic plasma extravasation and the chemosensitivity of the cornea were greatly diminished already 10 min after systemic capsaicin treatment, i.e. at a time when the substance P content of the peripheral nerve was still unchanged. These early effects of systemic capsaicin treatment are therefore caused by actions other than depletion of substance P.
