The effects of OB-induced depression on nociceptive behaviors induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus

A bi-directional relationship between depression and migraine has been widely reported in epidemiological and clinical studies, but the mechanisms of interaction between these disorders have not been fully examined using animal models. The aim of the present study was to investigate the effects of depression elicited by olfactory bulbectomy (OB) on trigeminovascular nociception in conscious rats. The nociception was induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus (SSS); this procedure causes nociception similar to that experienced during vascular headaches such as migraine. We showed that nociceptive behaviors (grooming and head flicks) were significantly enhanced in OB rats as compared to sham-operation (Sham) rats and that these nociceptive behaviors were correlated with depressive-like behaviors. Systemic administration of the antidepressant amitriptyline (AMI) significantly alleviated nociceptive behaviors in both the OB rats and Sham rats. Plasma levels of substance P (SP), but not plasma calcitonin gene-related protein (CGRP), significantly increased in OB rats and plasma SP levels decreased to normal following AMI treatment. Furthermore, changes in plasma SP levels were associated with both depressive-like behaviors and nociceptive behaviors. In conclusion, our results indicate that OB-induced depression can exacerbate trigeminovascular nociception, which may be mediated by SP. Moreover, we demonstrate that inhibition of SP release may contribute to the antinociceptive effect of AMI.

► This is the first time using animal model to investigate the effects of depression on trigeminovascular nociception.
► The depression can exacerbate nociceptive behaviors induced by electrical stimulation of the dura mater in OB rats.
► SP is crucially involved in the effects of depression on nociceptive behaviors.
► The inhibition of SP release may contribute to the observed antinociceptive effect of amitriptyline.