Protracted hypomobility in the absence of trigeminal sensitization after cortical spreading depolarization: Relevance to migraine postdrome

Mamoru Shibata,Satoshi Kitagawa,Chunghua Tang,Miyuki Unekawa,Yohei Kayama,Toshihiko Shimizu,Jin Nakahara,Norihiro Suzuki

doi:10.1016/j.neures.2021.03.010

Mamoru Shibata, Satoshi Kitagawa + Show 6 more

Open Access

https://doi.org/10.1016/j.neures.2021.03.010

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Abstract

Migraine sufferers often exhibit photophobia and physical hypoactivity in the postdrome and interictal periods, for which no effective therapy currently exists. Cortical spreading depolarization (CSD) is a neural phenomenon underlying migraine aura. We previously reported that CSD induced trigeminal sensitization, photophobia, and hypomobility at 24 h in mice. Here, we examined the effects of CSD induction on light sensitivity and physical activity in mice at 48 h and 72 h. Trigeminal sensitization was absent at both time points. CSD-subjected mice exhibited significantly less ambulatory time in both light (P = 0.0074, the Bonferroni test) and dark (P = 0.0354, the Bonferroni test) zones than sham-operated mice at 72 h. CSD-subjected mice also exhibited a significantly shorter ambulatory distance in the light zone at 72 h than sham-operated mice (P = 0.0151, the Bonferroni test). Neurotropin® is used for the management of chronic pain disorders, mainly in Asian countries. The CSD-induced reductions in ambulatory time and distance in the light zone at 72 h were reversed by Neurotropin® at 0.27 NU/kg. Our experimental model seems to recapitulate migraine-associated clinical features observed in the postdrome and interictal periods. Moreover, Neurotropin® may be effective in ameliorating postdromal/interictal hypoactivity, especially in a light environment.

Highlights

Migraine is a debilitating chronic neurological disorder characterized by recurrent headache attacks accompanied by nausea/vomiting and heightened sensitivity to light and sound (Headache Classification Committee of the International HeadacheSociety, 2018)
We previously demonstrated that Cortical spreading depolarization (CSD) caused trigeminal sensitization, photophobia, and hypoactivity in both light and dark zones at 24 h in mice, all of which were ameliorated by anti-migraine agents, sumatriptan and olcegepant (Tang et al, 2020)
There was no significant effect of Neurotropin® administration on CSD-related electrophysiological parameters

Summary

Introduction

Migraine is a debilitating chronic neurological disorder characterized by recurrent headache attacks accompanied by nausea/vomiting and heightened sensitivity to light and sound (Headache Classification Committee of the International HeadacheSociety, 2018). People with migraine suffer most during the headache phase, neurological symptoms are known to persist in the postdrome and interictal phases (de Tommaso et al, 2014; May, 2017). It has been shown that abnormal sensitivity to light (photophobia) and ocular allodynia are present in both ictal and interictal phases of migraine (Chu et al, 2011; McAdams et al., 2020; Mulleners et al, 2001; Perenboom et al, 2018). These symptoms can make working in a light environment more difficult.

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