IADR Abstract Archives
Continuous Sumatriptan Causes Increased Excitability in the Rat Trigeminal System
Objectives: Migraine remains poorly understood, despite being the third most common and disabling disease in the world, with a global prevalence of 10%. We have recently developed a novel clinically-relevant model of migraine that uses continuous sumatriptan administration to induce a migraine-like state. This model was used to investigate the hypothesis that the appearance of migraine symptoms, such as the development of facial allodynia and increased responses to migraine triggers, are associated with peripheral and central sensitisation of the trigeminovascular system.
Methods: The trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were harvested from rats following subcutaneous infusion with sumatriptan or saline (over a period of 6 days), either on the last day of infusion (day 6) (n=4) or on day 20 (from the start of infusion) (n=2). A subgroup of the animals culled on day 20 were treated with sodium nitroprusside (a nitric oxide donor known to trigger migraine in humans) prior to tissue collection (n=2). Tissues were immunohistochemically labelled using antibodies to identify known biomarkers of neuronal and glial activation and specific cell types (pERK, pp38, Iba-1, GFAP and NeuN).
Results: An increase in biomarker expression was observed in sumatriptan-infused rats in both the TG and TNC at day 6 and day 20. In the TNC, this expression was localised to areas known to be involved in nociceptive processing in migraine. Labelling for pERK and pp38 displayed a shift in expression from neurones (on day 6) to glia (on day 20), implicating a role for both of these cell types in migraine.
Conclusions: Continuous sumatriptan administration causes increased expression of markers of altered excitability in neuronal and glial cells in both the TG and TNC. This suggests that both peripheral and central sensitisation of the rat trigeminovascular system are involved in the pathophysiological mechanism underlying migraine.
Methods: The trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were harvested from rats following subcutaneous infusion with sumatriptan or saline (over a period of 6 days), either on the last day of infusion (day 6) (n=4) or on day 20 (from the start of infusion) (n=2). A subgroup of the animals culled on day 20 were treated with sodium nitroprusside (a nitric oxide donor known to trigger migraine in humans) prior to tissue collection (n=2). Tissues were immunohistochemically labelled using antibodies to identify known biomarkers of neuronal and glial activation and specific cell types (pERK, pp38, Iba-1, GFAP and NeuN).
Results: An increase in biomarker expression was observed in sumatriptan-infused rats in both the TG and TNC at day 6 and day 20. In the TNC, this expression was localised to areas known to be involved in nociceptive processing in migraine. Labelling for pERK and pp38 displayed a shift in expression from neurones (on day 6) to glia (on day 20), implicating a role for both of these cell types in migraine.
Conclusions: Continuous sumatriptan administration causes increased expression of markers of altered excitability in neuronal and glial cells in both the TG and TNC. This suggests that both peripheral and central sensitisation of the rat trigeminovascular system are involved in the pathophysiological mechanism underlying migraine.