Roles of Neuropeptide S in Anesthesia, Analgesia, and Sleep

Abstract

Neuropeptide S (NPS) is an endogenous peptide that regulates various physiological functions, such as immune functions, anxiety-like behaviors, learning and memory, the sleep-wake rhythm, ingestion, energy balance, and drug addiction. These processes include the NPS receptor (NPSR1). The NPS-NPSR1 system is also significantly associated with the onset of disease, as well as these physiologic functions. For example, NPS is involved in bronchial asthma, anxiety and awakening disorders, and rheumatoid arthritis. In this review, among the various functions, we focus on the role of NPS in anesthesia-induced loss of consciousness; analgesia, mainly by anesthesia; and sleep-wakefulness. Progress in the field regarding the functions of endogenous peptides in the brain, including NPS, suggests that these three domains share common mechanisms. Further NPS research will help to elucidate in detail how these three domains interact with each other in their functions, and may contribute to improving the quality of medical care.

Keywords: Neuropeptide S; Neuropeptide S receptor (NPSR1); analgesia; anesthesia; sleep.

Figure 1

NPS orchestrates an endogenous sleep–wakefulness circuit. Activation of locus coeruleus results in excitation of the thalamus, then cerebral cortex activation. This sequential process facilitates wakefulness. VLPO inhibits wakefulness by LC depression. NPS activates the hypothalamus and LC but inhibits VLPO. NPS could play a role as a conductor which orchestrates these sleep–wakefulness-related brain structure–activity relationships to promote quantified sleep rhythm. The solid line indicates an exciting process, while the dotted line denotes inhibition; LC, the locus coeruleus; VLPO, the ventrolateral preoptic area.

Figure 2

(A) Conventionally, there is a weak link among anesthesia-induced unconsciousness, physiological sleep, and analgesia. (B) The physiological functions of endogenous peptides in the brain, including NPS, suggest that they share common mechanisms. A study of the role of NPS in these three domains will help to determine the details of how these three domains interact with each other.