Kisspeptin modulates pain sensitivity of CFLP mice

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.

Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

“…It has been discovered that kisspeptin attenuates morphine effect [28], and is expressed in the NAc [44], pointing to its possible involvement in the regulation of mesocorticolimbic dopaminergic activity. Interestingly, the centers of reward and addiction have also been implicated in the regulation of locomotion.…”

Kisspeptin leads to calcium signaling in cultured rat dorsal root ganglion neurons

“…It has been reported that central administration of kisspeptin-13 to rodents causes nociceptive effects (Spampinato et al 2011;Elhabazi et al 2013;Csabafi et al 2018). The activation of KISS1R has been shown to result in calcium mobilization and recruitment of mitogen-activated protein kinases (MAPKs) such as the extracellular signal-regulated kinases (ERK) and p38 (Castano et al 2009).…”

The acute phase response in bats (Carollia perspicillata) varied with the time and dose of the immune-challenge

“…The experimental trials were conducted on the climatic chamber with 6 individuals at a time, and the bats were assigned to only one period and dose treatments. The range of LPS doses represent the maximum dose used in previous studies with bats (5 mg/kg LPS - Stockmaier et al 2015; 2018) and doses at least two to three times that value.…”

“…Three-way mixed ANOVA (2 Between subject factors / 1Within subject factor) were used to test for the interaction effects of dose (PBS, 5 mg/kg LPS, 10 mg/kg LPS, and 15 mg/kg LPS) and time of injection (resting or activity) as between subject factors, and time (ΔTb for 12 hours) as within subject factors on skin temperature change (ΔTb). When three-way interaction or two-way interaction were significant, simple main effect of factors (dose, time of injections and time) were tested by a Bonferroni post-hoc test for pairwise means comparisons (Rygula et al 2006; Csabafi et al 2018; Cohen et al 2020; Guan et al 2020; Sun et al 2021). Main effect Three-way mixed ANOVA were interpreted in the absence of statistically significant interactions (Maxwell and Delaney 2004; Kiernan 2014) by Tukey HSD or Bonferroni post-hoc test for pairwise comparisons when applicable.…”

“…Leukocytosis in bats is associated with increased circulating neutrophils (Weise et al 2017), whereas the N/L ratio increased after LPS injection with similar doses of LPS during the active or resting phases (Stockmaier et al 2018; Cabrera-Martinez et al 2019; Melhado et al 2020). Although most of these studies reported body mass loss 24 hours after LPS injections and assumed that it is partly due to anorexia, not all examined the effect of LPS on food intake rate (Schneeberger et al 2013; Stockmaier et al 2015, 2018; Guerrero-Chacón et al 2018).…”