Abstract
Migraine is one of the most common and disabling diseases in the world. A major feature of migraine headache is its aggravation by maneuvers that momentarily increase intracranial pressure. A key hypothesis implicates mechanical sensitization of trigeminal afferents that innervate the intracranial meninges in mediating this feature of migraine. However, whether such pain-related neural response actually develops under endogenous conditions that are linked specifically to migraine remains to be established. Single-unit recordings in the trigeminal ganglion of anesthetized male rats were combined with quantitative mechanical stimulation of the cranial dura mater to determine whether cortical spreading depression (CSD) – an endogenous migraine triggering event - affects the mechanosensitivity of meningeal afferents. CSD gave rise to an almost threefold increase in the magnitude of the responses to mechanical stimuli in 17/23 of the afferents tested. CSD-evoked meningeal afferent mechanosensitization occurred with a delay of 23.1±2.2 min and lasted 64.1±6.8 min in recording sessions that lasted for 90 minutes and for 177.5±22.1 min in recording sessions that were extended for 240 min. Some of the sensitized afferents also developed a shorter-lasting increase in their ongoing discharge rate, which was not correlated with the increase in their mechanosensitivity, suggesting that CSD-evoked meningeal afferent sensitization and increase in ongoing activity are independent phenomena. These novel findings support the notion that mechanical sensitization of meningeal afferents serves as a key nociceptive process that underlies the worsening of migraine headache during conditions that momentarily increase intracranial pressure.
Significant Statement Migraine headache is associated with symptoms suggestive of exaggerated intracranial mechanosensitivity. Enhanced mechanosensitivity of meningeal afferents could mediate this migraine feature, but whether such neural response occurs under endogenous conditions linked specifically to migraine remains a matter of speculation. Elicitation of cortical spreading depression (CSD), an endogenous migraine trigger led to a pronounced and persistent increase in the mechanosensitivity of meningeal afferents, which was not correlated with the additional shorter-lasting increases in the afferents’ ongoing activity. Mechanosensitization of meningeal afferents, induced by CSD and possibly other migraine triggers, could serve as a key nociceptive process that underlies the intracranial pain of migraine headache and its worsening during conditions that momentarily increase intracranial pressure, such as rapid head movements and coughing.
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