Effects of UCMS-induced depression on nociceptive behaviors induced by electrical stimulation of the dura mater

The comorbidity between migraine and depression not only provides a major treatment challenge, but also represents a heavy burden on society. However, the relationship between depression and migraine and their molecular biological mechanisms remain unclear. This study investigated the effects of depression elicited by unpredictable chronic mild stress (UCMS) on trigeminovascular nociception in conscious rats and detected a concentration of calcitonin gene-related peptide (CGRP) and substance P (SP) in the external jugular vein. We divided the rats into four groups: control-stimulated (C/S), control-nonstimulated (C/NS), UCMS-stimulated (U/S), and UCMS-nonstimulated (U/NS). We stimulated the dura mater adjacent to the superior sagittal sinus of rats in the C/S and U/S groups and observed their nociceptive behaviors. We found significant differences between the UCMS and control groups in weight, sucrose preference, and locomotor behavior. Nociceptive behaviors (number of head flicks and head-turning time) were significantly increased in the U/S compared with the C/S group, and head-turning time correlated with depressive-like behaviors. The plasma level of SP was increased significantly in the U/NS compared with the C/NS group. However, no significant differences involving the other groups were observed. UCMS-induced depression can exacerbate trigeminovascular nociception, making rats more sensitive to pain.