Kisspeptin-13 induces hyperalgesia and modulates the expression of opioid and glutamate receptors in mice.

Kisspeptins are hypothalamic neuropeptides well known for their role in reproductive biology. Our previous results have demonstrated that kisspeptin-13 (KP-13) has pronociceptive and anti-opioid effects. In our present experiments, we investigated the effects of KP-13 on nociception under both physiological and inflammatory conditions, as well as on the gene expression of regions involved in mediating pain sensation in C57BL/6 mice. Different doses of KP-13 were administered to adult male C57BL/6 mice, and either the tail-flick latency was measured in the tail-flick test or the time spent with nocifensive behavior was determined in the formalin test. In another group of animals, after KP-13 treatment, qPCR was used to determine the relative gene expression of Oprd1, Oprk1, Oprm1, Grin1, Grin2b, Grin2d, and Grm5 in samples of the dorsal root ganglion (DRG), amygdala, hypothalamus, and anterior cingulate cortex (ACC). Our results showed that KP-13 treatment decreased the tail-flick latency in a dose-dependent manner. In the formalin test, the KP-13-treated group showed increased nocifensive behavior compared to the control group. In DRG, KP-13 caused upregulation of Oprd1 and downregulation of Oprk1. In the amygdala, KP-13 decreased the expression of Oprd1 and Grin2b. In the hypothalamus, both Oprm1 and Oprd1 were downregulated. In the ACC, Oprk1 and Grm5 expression increased, whereas a decrease in Grin2b expression was observed. In conclusion, our results suggest that KP-13 has a hyperalgesic effect, which may be mediated by region-specific alterations in the gene expression of opioid and glutamate receptors.