Orexin-1 receptors in the rostral ventromedial medulla are involved in the modulation of capsaicin evoked pulpal nociception and impairment of learning and memory.

AIM: To investigate the role of rostral ventromedial medulla orexin-1 receptors in the modulation of orofacial nociception as well as nociception-induced learning and memory impairment in adult male rats.

METHODOLOGY: Pulpal nociception was induced by intradental application of capsaicin (100 μg) into the incisors of rats. Orexin-1 receptors agonist (orexin-A, 10, 25 and 50 pmol L-1  rat-1 ) and antagonist (SB-334867-A, 40 and 80 nmol L-1  rat-1 ) were microinjected into the rostral ventromedial medulla prior to capsaicin administration. Total time spent on nocifensive behaviour was recorded by direct visualization of freely moving rats whilst learning and memory were evaluated by the Morris water maze test. One-way analysis of variance and repeated-measures were used for the statistical analysis.

RESULTS: Capsaicin-treated rats had a significant increase of nocifensive behaviours (P < 0.001), as well as learning and memory impairment (P < 0.001). However, intraventromedial medulla prior micro-injection of orexin-A (50 pmol L-1  rat-1 ) significantly reduced the nociceptive behaviour (P < 0.001). This effect was blocked by pre-treatment with SB334867-A (80 nmol L-1  rat-1 ). Orexin-A (50 pmol L-1  rat-1 ) also inhibited nociception-induced learning and memory deficits. Moreover, administration of SB-334867-A (80 nmol L-1  rat-1 ) plus orexin-A (50 pmol L-1  rat-1 ) had no effect on learning and memory deficits induced by capsaicin.

CONCLUSIONS: The data suggest that rostral ventromedial medulla orexin-A receptors are involved in pulpal nociceptive modulation and improvement of learning and memory deficits induced by intradental application of capsaicin.