Nitric oxide in cerebral vasodilation and headache

research providing evidence that dura mater does not represent a mere covering to the central nervous system. The evidence provided by the authors is that CSD reduces blood flow in the dura mater and the hypothesis is that such reduction reflects metabolic changes in the brain via connections between cortical and dural blood supplies. The relevance of the finding is the possible activation of nociceptive fibers in the dura mater. In 1993, Piper et al. (1) reported no increase in CGRP plasma level from the cephalic circulation following CSD in the cat. Those findings suggested that CSD per se was not a sufficient trigger factor for CGRP release from trigeminovascular fibers. Nevertheless, as quoted by Lambert and Michalicek in the present article, CSD in the rat was sufficient to increase c-fos expression in trigeminal nuclei, an increase that was secondary to trigeminal fiber activation (2). Changes in dural blood flow described herein were not critical; however, they might be enough for stimulation of the trigeminovascular system. Orthodromic stimulation might increase c-fos expression in brainstem trigeminal nuclei, whereas antidromic stimulation might induce neurogenic inflammation in peripheral tissues. The data in the article indicate an interesting link between physiological events in the brain and its "capsule". At the present time, however, clinical evidence for such events in humans is lacking. Furthermore, as recently reviewed by Lauritzen (3) the role of CSD in migraine remains theoretical.