Calcineurin inhibitor-induced headache: Clinical characteristics and possible mechanisms

Uta Ferrari, Monika Empl, Kwang Sik Kim, Petra Sostak, Stefanie Förderreuther, Andreas Straube

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)211-214
Number of pages4
Issue number3
StatePublished - Mar 1 2005


  • Calcineurin inhibitors
  • Headache
  • Human cerebral endothelial cells
  • Immune suppression
  • Nitric oxide
  • Organ transplantation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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