Apelin signalling in the periaqueductal grey matter alleviates capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rat

Abstract

AbstractAimPulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra‐periaqueductal grey matter (PAG) administrations of Apl‐13 on capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rats.MethodologyForty‐nine male Wistar rats (200–250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra‐PAG injection of Apl‐13 (1, 2 and 3 μg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a μ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One‐way analysis of variance followed by Tukey post hoc tests was used for statistical analysis.ResultsIntra‐PAG administration of Apl‐13 significantly reduced the capsaicin‐induced nocifensive behaviour (p < .01). This antinociception effect was inhibited by F13A and naloxone. Apl‐13 inhibited nociception‐induced learning and memory deficits (p < .01). The cognitive effects were also blocked by pre‐treatment administration of F13A (3 μg/rat).ConclusionsThese findings indicated that Apl‐13, via Apl receptors (AR or APJ) and μ opioid receptors, alleviated capsaicin‐induced dental nocifensive behaviour and protected against nociception‐induced learning and memory impairments. As a result of our findings, Apl appears to be a promising analgesic option for further research in orofacial pain models and clinical trials.