Effect of nitric oxide on substance P release from the peripheral endings of primary afferent neurons

To elucidate the interaction between nitric oxide (NO) and substance P (SP) in neurogenic inflammatory responses, we studied the effect of drugs relat ed to nitric oxide (NO) on the levels of Eva ns blue a nd SP released into perfusate from the subcutaneous space in the rat instep. Noxious heat stimu lation (47 degrees C for 30 min) caused an increase in SP release in parall el with plasma extravagation. N-W-nitro-L-arginine methylester (L-NAME: 100 mg/kg, once daily) given intraperitoneally (i.p.) five times (chronic trea tment) significantly suppressed the heat-evoked SP release and Evans blue l eakage. FK409 (10(-4) M), which evokes a release of NO, applied locally cau sed a remarkable increase in the SP release into the perfusate. These resul ts suggest that heat-induced NO generation causes SP release from the perip heral endings of small-diameter primary afferent neurons. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.