To ascertain whether chronic exposure to nerve growth factor (NGF) alters the responsiveness of sensory neurons to prostaglandin E(2) (PGE(2)), sensory neurons taken from adult rats were grown in culture in the presence or absence of NGF for 7 days. Neurons then were exposed to PGE(2) and release of immunoreactive calcitonin gene-related peptide (iCGRP) and production of immunoreactive cAMP (icAMP) were examined. Growing neurons in the presence of 250 ng/ml NGF increased the content and the release of iCGRP from sensory neurons. Independent of NGF treatment, exposure to 100 nM PGE(2) augmented capsaicin- or potassium-stimulated release of iCGRP by 1. 5-fold compared with cells not exposed to PGE(2). In a similar manner, NGF treatment did not alter the ability of PGE(2) to increase the content of icAMP. These data suggest that prostaglandin-induced sensitization of sensory neurons is not influenced by NGF.