Multiphasic morphine modulation of substance P release from capsaicin-sensitive primary afferent fibers

Morphine produces a multiphasic modulation of K+-evoked substance P release from trigeminal slices and dorsal root ganglion neurons in culture. We now found that the C-fiber stimulant, capsaicin (1 mu M), evoked release of su bstance P that was inhibited, enhanced and inhibited by 0.1 nM, 1 mu M, and 10 mu M morphine, respectively. This morphine's multiphasic effect was blo cked by naloxone (100 nM). Neonatal treatment with capsaicin produced therm al hypoalgesia and abolished the multiphasic effect of morphine on substanc e P release evoked by 50 mM K+. These findings suggest that the multiphasic modulation of substance P release by morphine is dependent on C-type affer ents and may be of relevance to nociception.