Editors' ChoiceNeurology

Depressed Brains Inflict Pain

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Science Translational Medicine  28 Jul 2010:
Vol. 2, Issue 42, pp. 42ec119
DOI: 10.1126/scitranslmed.3001507

Migraine headaches cause great suffering and disability for those afflicted with this common neurovascular disorder. The aura that typically heralds a migraine attack and is a signature of this illness has been attributed to waves of depression in the spontaneous electrical activity of cortical neurons, known as cortical spreading depression (CSD). However, it has remained unclear whether this phenomenon is merely coincident with, or rather has an etiological link, to the headache that follows. Zhang and colleagues have offered intriguing evidence that the classic migraine headache is in fact triggered by this spreading depression. Studying anesthetized rats in vivo, they measured the electrical activity of single neurons that serve as pain receptors in the meninges, the tissue that encapsulates the brain and serves as the site of headache onset. These cells were monitored before and during the induction of CSD on the cortical surface of the brain.

In response to three different methods to induce CSD, the electrical activity of the meningeal pain receptors was increased in half of the stimulation trials in a dramatic and long-lasting manner, at least 37 min on average, and often up to the maximum recording time of over 1 hour. Neuronal activation responses measured in the ganglion of the trigeminal nerve, which contains the meningeal pain receptors, were observed both with short delays (before or during the CSD wave) or longer delays (averaging 12 min after the CSD wave), possibly reflecting different pain receptor subpopulations. In two-thirds of the stimulation trials, long-lasting activation of the pain receptors followed the minute-long wave of CSD over the cortex by about 14 min. This delay approximates the latency between CSD and the reduced cortical blood flow observed in human imaging studies, as well as the latency between the aura and the sustained incapacitating headache experienced by migraine sufferers. As the authors indicate, these findings suggest that blocking the delayed induction of pain receptors in the meninges during the signature aura phase of the attack may hold promise in the development of new interventions for this disabling illness.

X. Zhang et al., Activation of meningeal nociceptors by cortical spreading depression: Implications for migraine with aura. J. Neurosci. 30, 8807–8814 (2010). [Abstract]

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