Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells

TY - JOUR

T1 - Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells

AU - Neeb, Lars

AU - Hellen, Peter

AU - Hoffmann, Jan

AU - Dirnagl, Ulrich

AU - Reuter, Uwe

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Methylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels in a cluster headache bout are normalized after a course of high dose corticosteroids. Here we assess whether MPD suppresses interleukin-1β (IL-1β)- and prostaglandin E2 (PGE2)-induced CGRP release in a cell culture model of trigeminal ganglia cells, which could account for the preventive effect in migraine and cluster headache. Metoprolol(MTP), a migraine preventive with a slow onset of action, was used for comparison.METHODS: Primary cultures of rat trigeminal ganglia were stimulated for 24 h with 10 ng/ml IL-1β or for 4 h with 10 μM PGE2 following the exposure to 10 or 100 μM MPD or 100 nM or 10 µM MTP for 45 min or 24 h. CGRP was determined by using a commercial enzyme immunoassay.RESULTS: MPD but not MTP blocked IL-1β-induced CGRP release from cultured trigeminal cells. PGE2-stimulated CGRP release from trigeminal ganglia cell culture was not affected by pre-stimulation whether with MPD or MTP.CONCLUSION: MPD but not MTP suppresses cytokine (IL-1β)-induced CGRP release from trigeminal ganglia cells. We propose that blockade of cytokine mediated trigeminal activation may represent a potential mechanism of action that mediates the preventive effect of MTP on cluster headache and recurrent migraine attacks.

AB - BACKGROUND: Methylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels in a cluster headache bout are normalized after a course of high dose corticosteroids. Here we assess whether MPD suppresses interleukin-1β (IL-1β)- and prostaglandin E2 (PGE2)-induced CGRP release in a cell culture model of trigeminal ganglia cells, which could account for the preventive effect in migraine and cluster headache. Metoprolol(MTP), a migraine preventive with a slow onset of action, was used for comparison.METHODS: Primary cultures of rat trigeminal ganglia were stimulated for 24 h with 10 ng/ml IL-1β or for 4 h with 10 μM PGE2 following the exposure to 10 or 100 μM MPD or 100 nM or 10 µM MTP for 45 min or 24 h. CGRP was determined by using a commercial enzyme immunoassay.RESULTS: MPD but not MTP blocked IL-1β-induced CGRP release from cultured trigeminal cells. PGE2-stimulated CGRP release from trigeminal ganglia cell culture was not affected by pre-stimulation whether with MPD or MTP.CONCLUSION: MPD but not MTP suppresses cytokine (IL-1β)-induced CGRP release from trigeminal ganglia cells. We propose that blockade of cytokine mediated trigeminal activation may represent a potential mechanism of action that mediates the preventive effect of MTP on cluster headache and recurrent migraine attacks.

KW - Adrenergic beta-1 Receptor Antagonists

KW - Animals

KW - Calcitonin Gene-Related Peptide

KW - Cells, Cultured

KW - Cluster Headache

KW - Dinoprostone

KW - Female

KW - Glucocorticoids

KW - Interleukin-1beta

KW - Male

KW - Methylprednisolone

KW - Metoprolol

KW - Migraine Disorders

KW - Rats

KW - Rats, Sprague-Dawley

KW - Trigeminal Ganglion

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/s10194-016-0609-x

DO - 10.1186/s10194-016-0609-x

M3 - SCORING: Journal article

C2 - 26931452

VL - 17

SP - 19

JO - J HEADACHE PAIN

JF - J HEADACHE PAIN

SN - 1129-2369

ER -