Abstract
To investigate a physiological function of substance P (SP) presenting in the peripheral ending of sensory neurons, we determined radioimmunoassayable SP (iSP) level in the subcutaneous perfusate and the volumes of edema evoked in rat paw by noxious heat stimulation simultaneously. Results obtained were as follows: Immersion of the rat paw into hot water (47°C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in the paw volume. The increasing effects were abolished after neonatal pretreatment with capsaicin, acute and chronic denervation of the sciatic and saphenous nerves. Intraplantal injection of SP evoked an increase in the paw volume in dose-dependent manner. This increasing effect of SP on the paw volume was more remarkable than that of histamine. The increase in the heat-evoked iSP release and edema volume were significantly inhibited by pretreatment with stem bromelain and emorfazone, and by pretreatmet with dexamethasone. A time lag was necessary for a manifestation of the inhibitory effect of dexamethasone, and this inhibitory effect of the steroid was abolished after the simultaneous application of actinomycin D.
These results suggest that (1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers and (2) bradykinin and prostaglandins 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.
