Gene for pain modulatory neuropeptide NPFF: Induction in spinal cord by noxious stimuli

Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated p eptides that were originally identified on the basis of similarity to the m olluscan neuropeptide FMRF-amide. They have been hypothesized to have wide- ranging functions in the mammalian central nervous system, including pain m odulation, opiate function, cardiovascular regulation, and neuroendocrine f unction. We have cloned the NPFF gene from human, bovine, rat, and mouse, a nd show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precur sor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the dis tribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up -regulated by a model for inflammatory pain (carrageenan injection), but no t by a model for neuropathic pain (lumbar nerve ligation), Our results conf irm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expr ession in mammalian brain. They also provide a context for the interpretati on of the pain-sensitizing effects of injections of these peptides that hav e been previously reported. Our results support a model for the role of the se peptides in pain regulation at the level of the spinal cord.