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

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

^*Corresponding author for this work

Life Sciences and Bioengineering

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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 painlike 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.

Original language	English
Pages (from-to)	360-363
Number of pages	4
Journal	Biological and Pharmaceutical Bulletin
Volume	45
Issue number	3
DOIs	https://doi.org/10.1248/bpb.b21-00933
State	Published - 2022/03

Keywords

Acute herpes zoster-associated pain
Allodynia
Fosphenytoin
Hyperalgesia
Spontaneous pain

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science

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10.1248/bpb.b21-00933

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title = "Fosphenytoin Alleviates Herpes Simplex Virus Infection-Induced Provoked and Spontaneous Pain-Like Behaviors in Mice",

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 painlike 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.",

keywords = "Acute herpes zoster-associated pain, Allodynia, Fosphenytoin, Hyperalgesia, Spontaneous pain",

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

year = "2022",

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doi = "10.1248/bpb.b21-00933",

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AU - Takasaki, Ichiro

AU - Nagashima, Ryota

AU - Ueda, Takahiro

AU - Ogata, Tomoki

AU - Inoue, Arata

AU - Shiraki, Kimiyasu

AU - Kitada, Yoshimi

AU - Arai, Saori

PY - 2022/3

Y1 - 2022/3

N2 - 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 painlike 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.

AB - 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 painlike 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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KW - Hyperalgesia

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Fosphenytoin Alleviates Herpes Simplex Virus Infection-Induced Provoked and Spontaneous Pain-Like Behaviors in Mice

Abstract

Keywords

ASJC Scopus subject areas

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