Fosphenytoin alleviates herpes simplex virus infection-induced provoked and spontaneous pain-like behaviors in mice

Ichiro Takasaki; Ryota Nagashima; Takahiro Ueda; Tomoki Ogata; Arata Inoue; Kimiyasu Shiraki; Yoshimi Kitada; Saori Arai

doi:10.1248/bpb.b21-00933

This article has now been updated. Please use the final version.

Fosphenytoin alleviates herpes simplex virus infection-induced provoked and spontaneous pain-like behaviors in mice

Ichiro Takasaki , Ryota Nagashima, Takahiro Ueda, Tomoki Ogata, Arata Inoue, Kimiyasu Shiraki, Yoshimi Kitada, Saori Arai

Author information

Ichiro Takasaki Corresponding author
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama
Graduate School of Innovative Life Sciences, University of Toyama
Ryota Nagashima
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama
Takahiro Ueda
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama
Tomoki Ogata
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama
Arata Inoue
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama
Kimiyasu Shiraki
Faculty of Nursing, Senri Kinran University
Yoshimi Kitada
Nobelpharma, Co., Ltd.
Saori Arai
Nobelpharma, Co., Ltd.

Keywords: Fosphenytoin, acute herpes zoster-associated pain, spontaneous pain, allodynia, hyperalgesia

JOURNAL FREE ACCESS Advance online publication

Article ID: b21-00933

DOI https://doi.org/10.1248/bpb.b21-00933

The final version of this article is now available: Vol. 45 (2022), No. 3 pp. 360-363

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Abstract

In this study, we investigated the effects of fosphenytoin (fPHT) a water-soluble prodrug of phenytoin, on the pain responses of a mouse herpes zoster (HZ) pain model. Transdermal herpes simplex virus type 1 (HSV-1) inoculation induced mechanical allodynia and hyperalgesia of the hind paw and spontaneous pain-like behaviors, such as licking the affected skin. Intravenous injection of fPHT (15 and 30 mg/kg) alleviated HSV-1-induced provoked pain (allodynia and hyperalgesia). The suppressive effects of fPHT on provoked pain were weaker than those of diclofenac and pregabalin which were used as positive controls. fPHT, diclofenac, and pregabalin significantly suppressed HSV-1-induced spontaneous pain-like behaviors. Among them, high-dose fPHT (30 mg/kg) showed the strongest suppression. Intravenous fPHT may become a viable option for an acute HZ pain, especially for spontaneous pain.

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