NPS is a 20 amino acid peptide identified as the endogenous ligand for the deorphanized GPR 154, currently named the NPSR (Xu et al., 2004). In situ hybridization studies have shown that NPS precursor mRNA is expressed in about 500 cells localized only in three brainstem regions; the peri-locus coeruleus area, the principal sensory trigeminal nucleus, and the lateral parabrachial nucleus [Figure 3; (Liu et al., 2011; Xu et al., 2007)]. A dense hypocretin/orexin fiber network surrounding NPS-positive cells has been described, suggesting the possibility of cross-talk between these two neuronal populations (Liu et al., 2011).