OBJECTIVE: To classify the headache syndromes under treatment with calcineurin inhibitors and to investigate whether the latter influence the nitric oxide production of human brain microvascular cells (HBMEC). BACKGROUND: Single cases of cyclosporine-induced headaches have been reported. Since calcineurin inhibitors are known to influence the renal metabolism of NO, a key molecule in tension-type headache and migraine, we were interested whether calcineurin inhibitors might change NO metabolism in HBMEC as well. DESIGN AND METHODS: Headache symptoms of 74 patients receiving cyclosporine and/or tacrolimus for organ transplantation were retrospectively assessed. Furthermore, the effect of cyclosporine and tacrolimus on nitric oxide production in human brain microvascular endothelial cells was investigated after incubation. RESULTS: Only 18 of the 74 patients reported no headache 1-36 months after liver, lung, or bone-marrow transplantation, 28 reported a new headache, and 17 an increase in the frequency or intensity of a pre-existing headache. The headache was generally classified as migraine without aura (IHS 1.1) or migraine-like headache (IHS 1.6). Furthermore, we found significantly increased NO production after co-incubation of calcineurin inhibitors with human brain microvascular endothelial cells. CONCLUSION: The pathophysiological mechanism of these headaches may be connected with an endothelial dysfunction in terms of increased production of NO.
OBJECTIVE: To classify the headache syndromes under treatment with calcineurin inhibitors and to investigate whether the latter influence the nitric oxide production of human brain microvascular cells (HBMEC). BACKGROUND: Single cases of cyclosporine-induced headaches have been reported. Since calcineurin inhibitors are known to influence the renal metabolism of NO, a key molecule in tension-type headache and migraine, we were interested whether calcineurin inhibitors might change NO metabolism in HBMEC as well. DESIGN AND METHODS: Headache symptoms of 74 patients receiving cyclosporine and/or tacrolimus for organ transplantation were retrospectively assessed. Furthermore, the effect of cyclosporine and tacrolimus on nitric oxide production in human brain microvascular endothelial cells was investigated after incubation. RESULTS: Only 18 of the 74 patients reported no headache 1-36 months after liver, lung, or bone-marrow transplantation, 28 reported a new headache, and 17 an increase in the frequency or intensity of a pre-existing headache. The headache was generally classified as migraine without aura (IHS 1.1) or migraine-like headache (IHS 1.6). Furthermore, we found significantly increased NO production after co-incubation of calcineurin inhibitors with human brain microvascular endothelial cells. CONCLUSION: The pathophysiological mechanism of these headaches may be connected with an endothelial dysfunction in terms of increased production of NO.
Authors: Ronald G Lafrenière; M Zameel Cader; Jean-François Poulin; Isabelle Andres-Enguix; Maryse Simoneau; Namrata Gupta; Karine Boisvert; François Lafrenière; Shannon McLaughlan; Marie-Pierre Dubé; Martin M Marcinkiewicz; Sreeram Ramagopalan; Olaf Ansorge; Bernard Brais; Jorge Sequeiros; Jose Maria Pereira-Monteiro; Lyn R Griffiths; Stephen J Tucker; George Ebers; Guy A Rouleau Journal: Nat Med Date: 2010-09-26 Impact factor: 53.440
Authors: Asha Nair; Manuela Simonetti; Nicol Birsa; Michel D Ferrari; Arn M J M van den Maagdenberg; Rashid Giniatullin; Andrea Nistri; Elsa Fabbretti Journal: Mol Pain Date: 2010-08-24 Impact factor: 3.395