The Research On The Role Of NPFF Systems In The Development Of Acute Neuroinflammation

There may be multiple pathways for induction of fever. Prostaglandin and endogenous glucocorticoids are involved in lipopolysaccharide-fever. Injection of lipopolysaccharide can induce a biphasic fever and pretreatment with capsaicin, an agonist at the vanilloid receptor, blocks the first phase of lipopolysaccharide-induced fever. Furthermore, CB1 receptor subtype plays a key role in the pathogenesis of lipopolysaccharide-fever, even endogenous opioid system.Neuropeptide FF (NPFF, FLFQPQRF-NH2) is an endogenous peptide known to modulate opioid activity in the mammalian, mainly in the central nervous system. Given the endogenous opioid system has found to be involved in the fever caused by lipopolysaccharide and the data of NPFF system's modulation of opioide activity, therefore, those data suggested a link between lipopolysaccharide-induced fever and NPFF systems. Using a model of acute neuroinflammation, we sought to determine the effects of NPFF systems on the fever induced by i.c.v. injection of lipopolysaccharide. According to the degree of fever induced by different doses of lipopolysaccharide, we determined to use 125ng lipopolysaccharide as the best dose to cause fever. Coinjected with different doses of NPFF (10 and 30nmol), the fever of lipopolysaccharide (125 ng) was not modified. Interestingly, the selective NPFF receptors antagonist RF9 (30 nmol) injected into the third ventricle failed to induce significant effect, but it decreased the fever of lipopolysaccharide (125 ng) after cerebral administration in mice.These results suggest that NPFF receptors activation is required for lipopolysaccharide to produce fever. This interaction is the first evidence that NPFF systems participate in the control of acute neuroinflammation in conscious animals. The realization that the NPFF systems may participate in the control of the process of neuroinflammation is a new concept and may well lead to a fruitful approach to identify novel therapies for neuroinflammatory conditions. For example, it may be possible to use a NPFF receptors antagonist as a therapeutic strategy to prevent and treat brain diseases associated with neuroinflammation.