VZV Foundation - A Decade Of Leadership In The Fight Against VZV Infections

	Oral Presentation Abstracts: 49 [49] NEUROTROPIN® MODULATES ALLODYNIA AND HYPERALGESIA INDUCED BY HSV-1 INFECTION: A POSSIBLE TREATMENT TO ZOSTER-ASSOCIATED PAIN *K. Fukuhara (1,2), T. Kitamura (2), I. Takasaki (3), M. Kurokawa (4), Y. Kuraishi (3) & K. Shiraki (4) (1) Inst. Bio-Active Sci., Nippon Zoki Pharm. Co., Ltd., Hyogo, Japan; (2) Dept. Physiol., (3) Dept. Applied Pharmacol. & (4) Dept. Virol., Toyama Med. and Pharm. Univ., Toyama, Japan A non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®, NTP) has been applied in Japan to the treatment of pain (e.g. allodynia and hyperalgesia) in patients suffering from PHN and reflex sympathetic dystrophy. It has been suggested that the analgesic effects of NTP are attributed, at least partially, to enhancement of descending pain inhibitory system. However, the analgesic mechanisms of NTP for pain including neuropathic pain such as PHN are not completely understood. We have recently developed a mouse model for herpetic pain that had zosteriform lesions caused by HSV-1 infection as a substitute for zoster by VZV. This animal model displays allodynia and hyperalgesia with zosteriform lesions similar to patients with zoster, which is useful for studying the mechanisms of acute herpetic pain and the actions of anti-neuropathic pain drugs. In the present study, we examined the effects of NTP on herpetic pain in both BALB/c (HSV-susceptible) and C57BL/6 (HSV-resistant) mice infected with HSV-1. Mechanical allodynia and hyperalgesia with zosteriform lesions in both mice developed from days 4 to 5 post-inoculation, and reached their peaks on days 7 to 8. Skin lesions, allodynia and hyperalgesia in BALB/c mice were severer than those in C57BL/6 mice. A single oral administration of NTP (50-200 NU/kg) on days 7 to 8 post-inoculation ameliorated dose-dependently allodynia and hyperalgesia in both mice. The results demonstrated that NTP improved HSV-1-induced herpetic pain in mice, and suggest that the validity of NTP treatment in both patients with herpetic pain or PHN. The analgesic mechanisms of NTP on herpetic pain will be discussed. Corresponding Author: K. Fukuhara, Ph.D., Develop. Res. Dept., Inst. of Bio-Active Sci., Nippon Zoki Pharm. Co., Ltd., Yashiro, Hyogo, 673-1461 Japan

[49]

NEUROTROPIN® MODULATES ALLODYNIA AND HYPERALGESIA INDUCED BY HSV-1 INFECTION: A POSSIBLE TREATMENT TO ZOSTER-ASSOCIATED PAIN

*K. Fukuhara (1,2), T. Kitamura (2), I. Takasaki (3), M. Kurokawa (4), Y. Kuraishi (3) & K. Shiraki (4)
(1) Inst. Bio-Active Sci., Nippon Zoki Pharm. Co., Ltd., Hyogo, Japan; (2) Dept. Physiol., (3) Dept. Applied Pharmacol. & (4) Dept. Virol., Toyama Med. and Pharm. Univ., Toyama, Japan

A non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®, NTP) has been applied in Japan to the treatment of pain (e.g. allodynia and hyperalgesia) in patients suffering from PHN and reflex sympathetic dystrophy. It has been suggested that the analgesic effects of NTP are attributed, at least partially, to enhancement of descending pain inhibitory system. However, the analgesic mechanisms of NTP for pain including neuropathic pain such as PHN are not completely understood. We have recently developed a mouse model for herpetic pain that had zosteriform lesions caused by HSV-1 infection as a substitute for zoster by VZV. This animal model displays allodynia and hyperalgesia with zosteriform lesions similar to patients with zoster, which is useful for studying the mechanisms of acute herpetic pain and the actions of anti-neuropathic pain drugs. In the present study, we examined the effects of NTP on herpetic pain in both BALB/c (HSV-susceptible) and C57BL/6 (HSV-resistant) mice infected with HSV-1.
Mechanical allodynia and hyperalgesia with zosteriform lesions in both mice developed from days 4 to 5 post-inoculation, and reached their peaks on days 7 to 8. Skin lesions, allodynia and hyperalgesia in BALB/c mice were severer than those in C57BL/6 mice. A single oral administration of NTP (50-200 NU/kg) on days 7 to 8 post-inoculation ameliorated dose-dependently allodynia and hyperalgesia in both mice. The results demonstrated that NTP improved HSV-1-induced herpetic pain in mice, and suggest that the validity of NTP treatment in both patients with herpetic pain or PHN. The analgesic mechanisms of NTP on herpetic pain will be discussed.

Corresponding Author: K. Fukuhara, Ph.D., Develop. Res. Dept., Inst. of Bio-Active Sci., Nippon Zoki Pharm. Co., Ltd., Yashiro, Hyogo, 673-1461 Japan