Several lines of evidence suggest that
neuropeptide FF (
NPFF) is involved in nociception and in the modulation of
opioid-mediated
analgesia. Following the identification of the precursor
protein for
NPFF, two
NPFF receptors and a second PQRF-NH(2) containing
peptide, termed NPVF, were identified. To further explore the functional role of PQRF-NH(2)
peptides, we have studied their distribution and also the regulation of
NPFF and NPVF systems in the spinal cord of rats with peripheral
inflammation. The distribution of
NPFF gene expression is very similar to that of
NPFF immunoreactive
peptide but is distinct from NPVF gene expression. In the rat spinal cord, gene expression of
NPFF but not that of NPVF was up-regulated by persistent
pain induced by
carrageenan inflammation. The distribution of
NPFF receptor 2 gene expression is very similar to that of the
NPFF peptide with a striking localization in the superficial layer of spinal cord. In rats with
carrageenan inflammation of the hind paw, expression of both
NPFF and
NPFF receptor 2 genes was up-regulated in the spinal cord, while expression of NPVF and
NPFF receptor 1 genes was not affected. The results of this study demonstrate a coordinated involvement of the spinal
NPFF system in the persistent
nociceptive pain states. Several studies have found a potentiation and prolongation of
morphine analgesia by
NPFF, therefore, it is highly possible that the endogenous spinal
NPFF system contributes to the enhanced
analgesic potency of
morphine in animals with peripheral
inflammation.