To investigate a physiological function of
substance P (SP) present in the peripheral ending of sensory neurons, we determined immunoreactive SP (iSP) levels in the s.c. perfusate and the amount of
edema evoked in rat paw by noxious heat stimulation. We found that immersion of rat paw into hot water (47 degrees C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in paw volume. Neonatal pretreatment with
capsaicin inhibited significantly the increase in both iSP and paw volume evoked by noxious heat stimulation. Acute and chronic
denervation of the sciatic and saphenous nerves also inhibited the heat-evoked iSP release and
edema remarkably. Intraplantar injection of SP evoked an increase in paw volume in dose-dependent manner. This increasing effect of SP on paw volume was more substantial than that produced by
histamine. Simultaneous treatment with
stem bromelain and
emorfazone decreased significantly the heat-evoked iSP release and
edema. These results suggest that 1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers with small-diameter, 2)
bradykinin may intervene in this SP release and 3) SP released in the periphery may be closely related to the
edema formation of the thermal injury reaction.