Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats

Abstract

Ghrelin is a peptide hormone released from the gastric endocrine glands and shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not been elucidated yet. The purpose of the study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [D-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adults rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance a 3-day cumulative dose regimen was used in rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg/kg), [D-Lys3]-GHRP-6 (10 mg/kg), and morphine (5 mg/kg) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [D-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Besides, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.

Effect of Thi̇ami̇ne on Morphi̇ne Analgesi̇a and Tolerance i̇n Rats

“…Prolonged use of opioids causes analgesic effects and side effects such as respiratory depression, euphoria, sedation, and nausea 25,26 . Different analgesic approaches, such as low-dose morphine or a mix of auxiliary medications, are utilized to lessen these unfavorable effects of morphine 27 . In this study, thiamine in analgesia tests, also known as B1vitaminin, increased morphine analgesia and reduced analgesic tolerance when combined with morphine.…”

“…ÇetindağÇiltaş et al / Cumhuriyet Medical Journal, 45(1):[25][26][27][28][29][30][31][32][33][34]2023 …”

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

“…Rats that did not respond after 15 seconds were removed from the experiment. The nociceptive response observed in the tail flick method is primarily attributed to the involvement of spinal mechanisms [ 20 , 21 ]. During the hot plate procedure, the rats were positioned on a heated plate set at a precise temperature of 53°C ± 0.5°C.…”

Ferroptosis Inhibitor Ferrostatin-1 Attenuates Morphine Tolerance Development in Rats by Inhibiting Dorsal Root Ganglion Neuronal Ferroptosis

“…Rats that did not reply after 15 seconds were removed from the experiment. The nociceptive response observed in the tail ick method is primarily attributed to the involvement of spinal mechanisms (Kanaan et al 1996, Baser et al 2020). During the hot plate procedure, the rats were positioned on a heated plate set at a precise temperature of 53 ± 0.5°C.…”