The possible roles of the
NPFF system in
pain processing are summarized from the viewpoints of (1)
biological activities of
NPFF, (2) anatomical distribution of
NPFF and its receptor(s) and (3) the regulation of
NPFF and receptor(s) in animal models of
pain.
NPFF and
NPFF analogues were found to have
analgesic, pronociceptive and
morphine modulating activities. Since the isolation of
NPFF, several other RF-NH2
peptides have been identified and some of them were found to have nociceptive or
morphine modulating activity. Depending on the pharmacological doses and locations of administration,
NPFF may exhibit the
biological activities of other structurally related RF-NH2
peptides thus complicating
NPFF bioactivity studies and their interpretation.
Acid sensing ion channels were found to respond to RF-NH2
peptides including
NPFF, raising the possibility that interaction of
NPFF and
acid sensing ion channels can modulate nociceptive activity.
NPFF and
NPFF receptor mRNAs are highly expressed and localized in the superficial layers of the dorsal cord, the two genes are also in dorsal root ganglia though at much lower level. The spinal
NPFF system is up-regulated by peripheral
inflammation in the rat. Furthermore, immunohistochemically,
NPFF receptor 2-protein was demonstrated to be increased in the primary afferents in the spinal cord of rats with peripheral
inflammation. Regulation and localization of spinal
NPFF systems, taken together with the
analgesic bioactivity of intrathecally administered
NPFF, strongly suggest involvement of spinal
NPFF system in
pain processing.