LAUSR

HighlightsEffect of kisspeptin‐13 (KP‐13) on pain sensation was studied in male and female CFLP mice.KP‐13 reduces the pain threshold independent of the sex of mice in the tail‐flick test possibly through KISS1R activation.In addition, KP‐13 reverses morphine analgesia and reduces acute morphine tolerance.It aggravates withdrawal signs precipitated by naloxone.Furthermore, KP‐13 induces hyperthermia. ABSTRACT Kisspeptin, a hypothalamic neuropeptide, is a member of the RF‐amide family, which have been known to modify pain sensitivity in rodents. The aim of the present study was to investigate the effect of kisspeptin‐13 (KP‐13), an endogenous derivative of kisspeptin, on nociception in adult male and female CFLP mice and the possible interaction of KP‐13 with morphine on nociception. Mice were injected with different doses of KP‐13, 30, 60 and 120 min after of which the nociceptive sensitivity were assessed via the tail‐flick test. To investigate the receptor involved in the mediation a kisspeptin receptor antagonist (KP‐234) pretreatment was applied before KP‐13 administration. Furthermore, we investigated the effect of KP‐13 on the acute antinociceptive effect of morphine, on acute morphine tolerance and on naloxone‐precipitated withdrawal. Last, the Von Frey test was used in order to assess KP‐13′s effect on mechanical nociception. Our results showed that KP‐13 decreased the nociceptive threshold of both males and females independent of sex, which was prevented by KP‐234. Furthermore, KP‐13 treatment depressed the acute antinociceptive effect of morphine and attenuated the development of morphine tolerance. KP‐13 also induced a mechanical hypersensitivity. These data underlie kisspeptin's hyperalgesic action and argues for the role of kisspeptin receptor 1 in the mediation of its action. Furthermore, our results suggest that central KP‐13 administration can modify the acute effects of morphine.