Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan

Abstract 

Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT_1B/D/F), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal “pain-sensory” fibers. However, as triptan receptors are also located on “pain-sensory” afferents throughout the body, it is surprising that triptans only reduce migraine pain in humans, and experimental cranial pain in animals. Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial, somatic and visceral pain in behavioral models in mice. Because sumatriptan must cross the blood brain barrier to reach somatic afferent terminals in the spinal cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless of route. However, in behavioral models of persistent inflammatory pain, we found a profound anti-hyperalgesic action of intrathecal, but not systemic, sumatriptan. By contrast, sumatriptan was completely ineffective in an experimental model of neuropathic pain. The pronounced activity of intrathecal sumatriptan against inflammatory pain in mice raises the possibility that there is a wider spectrum of therapeutic indications for triptans beyond headache.

Abbreviations: BBB, blood brain barrier, 5-HT, serotonin, DCVs, dense core vesicles, SC, subcutaneous, IT, intrathecal, 5-HT_1D-IR, 5-HT_1D receptor immunoreactivity

Keywords: Migraine, Headache, Inflammation, Serotonin, Sumatriptan, Intrathecal, Blood brain barrier