The Studies On The Antinociceptive Effects Of Neuropeptide S In The Mouse Formalin Test

Neuropeptide S (NPS), a recently discovered bioactive peptide, was reported to regulate sleep and arousal, mood, locomotion, feeding behaviors, learn and memory, and drug addiction. NPS receptor (NPSR) mRNA was found in several brain regions related to descending control system of pain, such as the periaqueductal gray (PAG), which suggested that NPS system could regulate pain transition. We first investigate the effect of NPS observed in the mouse formalin test, a model of inflammatory pain. NPS (0.1-100 pmol) administrated intracerebroventricularly (i.c.v.) dose-dependently attenuated both first-phase and second-phase nociceptive behaviors induced by paw formalin injection. NPS-elicited antinociceptive effect in the formalin test was counteracted by co-injection with peptidergic NPSR antagonist [D-Val5]NPS (1000 and 10000 pmol, i.c.v.) and NPS (10 pmol, i.c.v.), while [D-Val5]NPS (1000 and 10000 pmol, i.c.v.) alone induced neither hyperalgesia nor antinociception. Under the same experimental conditions, naloxone (i.p.,10 mg/kg) did not affect the antinociception induced by NPS (10 pmol, i.c.v.), but attenuated the antinociceptive effect induced by morphine (1000 pmol, i.c.v.). Furthermore, compared to the saline (i.c.v.) treated group, NPS (10 pmol, i.c.v.) treated group increased c-fos protein expression in nearly all subdivisions of the PAG in the formal in-injected mice. All the above results revealed that inhibition of inflammatory pain by NPS was through NPSR but not opioid receptors, and may be involved in the activation of PAG, suggesting that NPS-NPSR system may be a potential target for developing new analgesic drugs.