Reversal of Inflammatory and Noninflammatory Visceral Pain by Central or Peripheral Actions of Sumatriptan

Background & Aims: Sumatriptan is used specifically to relieve headache pain. The possible efficacy of sumatriptan was investigated in 2 models of visceral pain. Methods: Pancreatic inflammation was induced by intravenous injection of dibutyltin dichloride. Noninflammatory irritable bowel syndrome was induced by intracolonic instillation of sodium butyrate. The effects of systemic sumatriptan on referred hypersensitivity were tested in both models. Effects of sumatriptan within the rostral ventromedial medulla (RVM), a site of descending modulation of visceral pain, was determined by (1) testing the effects of RVM administration of 5HT1_B/D antagonists on systemic sumatriptan action and (2) determining whether RVM application of sumatriptan reproduced the actions of systemic drug administration. Results: Systemic sumatriptan elicited a dose- and time-related blockade of referred hypersensitivity in both models that was blocked by systemic administration of either 5HT1_B or 5HT1_D antagonists. Sumatriptan administered into the RVM similarly produced dose- and time-related blockade of referred hypersensitivity in both visceral pain models. This was blocked by local microinjection of the 5HT1_B antagonist but not the 5HT1_D antagonist. Microinjection of 5HT1_B or 5HT1_D antagonists into the RVM did not block the effects of systemic sumatriptan. Conclusions: Our findings suggest that sumatriptan suppresses either inflammatory or noninflammatory visceral pain, most likely through peripheral 5HT1_B/_D receptors. Actions at 5HT1_B receptors within the RVM offer an additional potential site of action for the modulation of visceral pain by triptans. These studies offer new insights into the development of strategies that may improve therapy of visceral pain conditions using already available medications.