The rostral ventromedial medulla orexin 1 receptors and extracellular signal-regulated kinase in hippocampus are involved in modulation of anxiety behavior induced by dental pulp nociception in adult male rats

Objectives: To explore the role of rostral ventromedial medulla (RVM) orexin 1 receptors (OX1R) on orofacial nociception -induced anxiety and locomotion in rats. Design: Forty two adult male Wistar rats (220–270 gr) were randomly divided into 7 groups (n = 6) as follows: untreated control, capsaicin, capsaicin vehicle-treated group (sham operation), capsaicin groups pretreated by intra-RVM administration orexin 1 receptor (OX1R) agonist (orexin A) or antagonist (SB-334867) and the capsaicin groups treated by drugs vehicles (DMSO or aCSF). Orofacial nociception was induced by intradental application of capsaicin (100 μg) into the incisors of rats. Anxiety level and locomotor activity were measured by the elevated plus maze (EPM) and open field (OF) tests, respectively. Hippocampal levels of phosphorylated extracellular signal regulated Kinase (p-ERK) was also assessed by western blotting. Results: Intradental application of capsaicin significantly increased anxiety and decreased locomotion behaviors. Intra-RVM microinjection of orexin-A significantly prevented capsaicin-induced anxiety-like behavior and increased locomotor activity in the EPM and OF tests. These effects were inhibited by SB-334867. Furthermore, orexin-A significantly increased p-ERK levels in capsaicin-treated rats. This effect was inhibited by pretreatment of the rats with SB-334867. Conclusions: The results suggest that both OX1R signaling in the RVM and hippocampal p-ERK signaling are involved in orofacial nociception-induced anxiety as well as locomotor activity.