The effect of trigeminal efferent stimulation on HPA axis

Objectives:The hypothalamic-pituitary-adrenocortical (HPA) axis is one of the common pathway of the stress response. This study was designed to determine the effect of pain stimulation through trigeminal nerve on HPA axis. Methods: Fourteen rats were injected capsaicin (30mM, n=7) or vehicle (control, n=7) to the tip of tongue innervated by trigeminal nerve (lingual nerve) under diethyl-ether inhalation anesthesia. Thirty min after the injection, blood samples from trunk, hypothalamic paraventricular nucleus (PVN), and pituitary glands were taken from the decapitated rats after coming out from the anesthesia. Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels were assayed by EIA kits, and mRNA expression of corticotrophin-releasing hormone (CRH) and proopiomelanocortin (POMC: a large protein precursor that originates ACTH), were evaluated using quantitative real-time PCR analysis. All animal experiments were conducted in accordance with international standards on animal welfare from the Animal Experiments Guidelines of the Institute for Animal Experimentation, Tohoku University.Results: ACTH levels in capsaicin group were significantly higher than those in vehicle group, while corticosterone levels had no change, indicating that this dose of capsaicin stimulation for 30 min was long enough to activate PVN and pituitary gland but not adrenal gland. Both CRH and POMC mRNA in capsaicin group were significantly higher than those in vehicle group, showing that tongue pain by capsaicin could induce stress related gene expression in cells of PVN and pituitary. Conclusion: Pain stress through trigeminal nerve activates HPA axis. This study was supported by a Grant-in -Aid for Scientific Research from the Japan Society for the Promotion of Science (19592401), and the Ministry of Education, Culture, Sports, Science and Technology (Scientific Research (C) 18592066).