IADR Abstract Archives
Altered brain activity in a pre-clinical model of cephalic pain
Objectives: Migraine is the third most prevalent, and sixth most disabling disease in the world. However, its neurobiology is not completely understood and treatments available are often inadequate. The current study aimed to investigate altered brain activity under migraine-like conditions, using a clinically relevant model of migraine in rats in combination with pre-clinical functional magnetic resonance imaging (fMRI).
Methods: Naïve rats underwent continuous subcutaneous administration of either sumatriptan (n=4) or saline (n=4) for 6 days. Under isoflurane anaesthesia, 7 Tesla MRI measurements were performed before (day 0), during (day 6) and after (day 20) sumatriptan administration to investigate changes in brain activity associated with development and subsequent recovery from allodynia.
Results: On day 6 of triptan infusion, the cerebral blood flow in grey matter structures was significantly reduced compared with that in saline-treated rats. Furthermore, in response to a stimulus train to the whisker pad region, rats showed a distinct, constant and unusually slow oscillation in the BOLD fMRI signal (standard GE-EPI sequence), occurring only in areas of superficial cortex and thalamus. The oscillation was not observed in saline-treated rats. Critically, at day 20 post-triptan administration, rats showed increased activity in response to whisker pad stimulation in deeper regions of the brain including brainstem and thalamus. Moreover, at day 20, sumatriptan- but not saline-treated rats showed high connectivity between the thalamus (seed region), the cortex and the brainstem.
Conclusions: Consistent with human data showing altered activity in the cortex and/or deeper regions of the migraineurs’ brain, the data from this study suggest that administration of sumatriptan results in MRI changes similar to those observed in humans, and that these are correlated with the development of allodynia. Thus, the use of this migraine model coupled with MRI techniques may facilitate the development of translational research advancing our understanding of migraine pathophysiology.
Methods: Naïve rats underwent continuous subcutaneous administration of either sumatriptan (n=4) or saline (n=4) for 6 days. Under isoflurane anaesthesia, 7 Tesla MRI measurements were performed before (day 0), during (day 6) and after (day 20) sumatriptan administration to investigate changes in brain activity associated with development and subsequent recovery from allodynia.
Results: On day 6 of triptan infusion, the cerebral blood flow in grey matter structures was significantly reduced compared with that in saline-treated rats. Furthermore, in response to a stimulus train to the whisker pad region, rats showed a distinct, constant and unusually slow oscillation in the BOLD fMRI signal (standard GE-EPI sequence), occurring only in areas of superficial cortex and thalamus. The oscillation was not observed in saline-treated rats. Critically, at day 20 post-triptan administration, rats showed increased activity in response to whisker pad stimulation in deeper regions of the brain including brainstem and thalamus. Moreover, at day 20, sumatriptan- but not saline-treated rats showed high connectivity between the thalamus (seed region), the cortex and the brainstem.
Conclusions: Consistent with human data showing altered activity in the cortex and/or deeper regions of the migraineurs’ brain, the data from this study suggest that administration of sumatriptan results in MRI changes similar to those observed in humans, and that these are correlated with the development of allodynia. Thus, the use of this migraine model coupled with MRI techniques may facilitate the development of translational research advancing our understanding of migraine pathophysiology.