CAPSAICIN-INDUCED RELEASE OF SUBSTANCE-P INCREASES COCHLEAR BLOOD-FLOW IN THE GUINEA-PIG

Physiological evidence from several studies suggests that endogenous v asoactive peptides, such as substance P (SP), and their respective rec eptor populations may participate in the mechanisms that govern the au toregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of a ction of SP. Capsaicin sensitivity has been used as a marker for senso ry neurons, and the release of SP following capsaicin treatment sugges ts a sensory transmitter role for SP. The present investigation examin es the relationship between the capsaicin-sensitive sensory neurons an d SP in the regulation of cochlear blood flow (CBF). In 75 pigmented g uinea pigs, the cochlea was surgically exposed and a laser Doppler flo wmeter probe placed on the bony surface of the first turn to monitor C BF. Capsaicin solutions (2 mu l, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increa se, without change in the systemic blood pressure. This effect could b e inhibited by application of a specific SP receptor antagonist, [D-Pr o(2),D-Trp(7,9)]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nm ol/2 mu l of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give ind irect evidence that SP is released from capsaicin-sensitive primary se nsory neurons.