Nerve growth factor antagonizes the neurotoxic action of capsaicin on primary sensory neurones

Abstract

The protein nerve growth factor (NGF) is a naturally occurring trophic substance for sympathetic neurones and for at least those primary sensory neurones containing substance P (refs 4-6). Thus retrogradely transported NGF increased substance P and protein content in corresponding dorsal root ganglia. Moreover, anti-NGF antibodies administered to newborn rats decreased substance P and somatostatin levels in dorsal root ganglia and dorsal spinal cord, suggesting an important role for NGF in the postnatal development of peptidergic sensory neurones. These neurones appear to be selectively affected by the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). Treatment of newborn rats with capsaicin led to degeneration of primary sensory neurones containing substance P, somatostatin, vasoactive intestinal polypeptide and cholecystokinin. The mechanism by which capsaicin evokes its neurotoxic effect is unknown. We report here that in newborn rats concomitant administration of NGF partially antagonized the deleterious effect of capsaicin on substance P-containing neurones in dorsal root ganglia as assessed by morphological and biochemical criteria. We conclude that capsaicin destroys the perikarya of primary sensory peptidergic neurones by interfering with the action of NGF, probably by blocking its retrograde axonal transport.