Rizatriptan effects on the cholecystokinin expression in endogenous pain modulatory system of a rat migraine model

Abstract

Objective To assess the influence of Rizatriptan on the cholecystokinin(CCK) expression in periaqueductal gray(PAG) of migraine model rat to investigate the possible mechanism by which Triptans treat migraine. Methods A total of 24 rats were randomly divided into four groups: normal control groups(A), migraine model groups(B), Rizatriptan control groups(C) and Rizatriptan treatment groups(D). C and D groups were intragastrically perfused with Rizatriptan, 1 mg/kg per day. After 7 days, nitroglycerin was subcutaneously injected into the buttocks of the B and D group to induce migraine. Two hours after nitroglycerin injection, the trigeminal ganglia were isolated.CGRP expression in periaqueductal gray were determined using SYBR Green I real-time quantitative PCR and Immunohistochemistry. Results CCK mRNA levels (target gene mRNA copies per 250 ng total RNA, ×106) in the rat midbrain of A, B, C, D groups were 1.25±0.41, 1.71±0.93, 0.17±0.12, 0.22±0.07 respectively. CCK-8-immunoreactive positive cells in the rat PAG of each group were 37.17±12.62, 40.17±11.09, 27.33±7.71, 20.67±7.66 respectively. CCK mRNA expression in group C was significantly lower than that of group A(P<0.05) while the CCK mRNA expression in group D was lower than that of group B(P<0.05). The CCK-8-positive cells of the rat PAG in group D were lower than that in group B(P<0.05). Conclusion Rizatriptan can down regulate the expression of CCK-8 in the PAG of the migraine rats and weaken the CCK-8 induced inhibition of the analgesic effects of opioid peptides. Key words: Rizatriptan; Migraine; Periaqueductal gray; Cholecystokinin