Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache?

The time course of propagation of scotoma and blood flow changes during mig raine aura parallels the phenomenon of cortical spreading depression (CSD). It was proposed that CSD generates a sterile neurogenic inflammation in th e meninges, which may then lead to the activation or sensitization of nocic eptors, thus generating headache. We performed rat experiments in which the effect of CSD on plasma extravasation in the dura mater and on neuronal ac tivity in deep laminae of the trigeminal nucleus was assessed in vivo. CSD did not alter dural plasma extravasation measured by means of bovine serum albumin-coupled flourescein (n = 17 rats) compared to the CSD-free contrala teral side. In an in vitro model, the application of KCI to the dura at con centrations extracellularly found during CSD did not alter the release of c alcitonin gene-related peptide and prostaglandin E-2 from the dura. In 33 r ats, neither single CSDs nor a series of CSDs altered ongoing neuronal acti vity or mechanical and/or thermal sensitivity of the deeply located neurons to stimulation of their receptive fields in the dura mater. These results are at variance with data that showed increased c-Fos labeling in superfici al laminae of the trigeminal nucleus following CSD, They do not suggest tha t CSD initiates migraine headache via neurogenic inflammation.