NPFF mediates the pain response by interaction with the NPFFR2. NPFF and its related RF-amide peptides in their interactions with NPFFR2 can also increase the neuronal activity of various areas of the hypothalamus to modulate the HPA axis, the autonomic nervous system, food intake, and energy homeostasis.
The underlying cellular mechanisms of these actions can now be explored because of the recent development of genomic and pharmacological tools. NPFFR2 signaling in part of the stress-modulation pathway induces depressive- and anxiety-like behaviors. NPFFR2 also regulates the energy homeostasis cascade to increase brown adipose tissue-mediated thermogenesis. This leads to benefiting body health and reduces the obese phenotypes.
NPFFR2 signaling might be a potential therapeutic target of stress- and obese-related disorders. Specific NPFF receptor agonists and antagonists have not been identified. Once this has occurred, it will lead to a better understanding of the function and signaling of the RF-amide peptides on specific receptors.
