Effects of Analgesics on Delayed Postherpetic Pain in Mice

2002 ◽  
Vol 96 (5) ◽  
pp. 1168-1174 ◽  
Author(s):  
Ichiro Takasaki ◽  
Atsushi Sasaki ◽  
Tsugunobu Andoh ◽  
Hiroshi Nojima ◽  
Kimiyasu Shiraki ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Postherpetic Neuralgia ◽  
Herpes Simplex Virus Infection ◽  
Skin Lesions ◽  
Cutaneous Lesions ◽  
Acyclovir Treatment ◽  
Simplex Virus ◽  
Von Frey Filaments

Background Postherpetic neuralgia is pain that persists long after the disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms of this delayed pain are unclear. Herpes simplex virus infection induces cutaneous lesions and pain-related responses in mice. The authors examined whether such responses would persist after the disappearance of the cutaneous lesions and whether some analgesics would be effective against them. Methods Female BALB/c mice were inoculated with herpes simplex virus type 1 on the unilateral hind paw. Pain-related responses of hind paw were determined using von Frey filaments. Beginning 5 days after inoculation, mice were given perorally the antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5 mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30 mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain-related responses were examined on days 25-35 after inoculation. Results Viral inoculation induced cutaneous lesions and pain-related responses beginning on day 5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after inoculation. Approximately half of the mice given acyclovir showed pain-related responses at least until day 40 after inoculation. Morphine, gabapentin, and mexiletine dose-dependently inhibited pain-related responses, but diclofenac had no effects. Conclusions The authors show a mouse model of delayed postherpetic pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia and the factors contributing to the transition from acute herpetic pain to delayed postherpetic pain. This may also be useful for the development of new analgesics against postherpetic neuralgia.

The possible relationship of herpes simplex virus infection to cause of retardation in severe mental handicap

1980 ◽  
Vol 10 (3) ◽  
pp. 555-557
Author(s):  
A. H. Reid ◽  
K. W. Martin ◽  
B. R. Ballinger ◽  
B. B. Heather
Keyword(s):  
Mental Retardation ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Infection ◽  
Research Findings ◽  
Simplex Virus ◽  
Antibody Levels ◽  
Relationship Of ◽  
The Relationship

SYNOPSISThe relationship between herpes simplex virus type 1 and mental retardation is explored by studying the antibody levels to this virus in a group of 86 severely and profoundly retarded adults. A tendency towards higher antibody levels is found in patients whose retardation is of unknown aetiology. The relationship of these observations to previous research findings and the possible significance of herpes simplex virus in the aetiology of mental retardation are discussed

scholarly journals Antiviral Activity of a Selective Ribonucleotide Reductase Inhibitor against Acyclovir-Resistant Herpes Simplex Virus Type 1 In Vivo

1998 ◽  
Vol 42 (7) ◽  
pp. 1629-1635 ◽  
Author(s):  
Jianmin Duan ◽  
Michel Liuzzi ◽  
William Paris ◽  
Michelle Lambert ◽  
Carol Lawetz ◽  
...  
Keyword(s):  
Drinking Water ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ribonucleotide Reductase ◽  
Cutaneous Lesions ◽  
Athymic Nude Mice ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The present study reports the activity of BILD 1633 SE against acyclovir (ACV)-resistant herpes simplex virus (HSV) infections in athymic nude (nu/nu) mice. BILD 1633 SE is a novel peptidomimetic inhibitor of HSV ribonucleotide reductase (RR). In vitro, it is more potent than ACV against several strains of wild-type as well as ACV-resistant HSV mutants. Its in vivo activity was tested against cutaneous viral infections in athymic nude mice infected with the ACV-resistant isolates HSV type 1 (HSV-1) dlsptk and PAAr5, which contain mutations in the viral thymidine kinase gene and the polymerase gene, respectively. Following cutaneous infection of athymic nude mice, both HSV-1 dlsptk and PAAr5 induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. A 10-day treatment regimen with ACV given topically four times a day as a 5% cream or orally at up to 5 mg/ml in drinking water was partially effective against HSV-1 PAAr5 infection with a reduction of the area under the concentration-time curve (AUC) of 34 to 48%. The effects of ACV against HSV-1 dlsptk infection were not significant when it was administered topically and were only marginal when it was given in drinking water. Treatment under identical conditions with 5% topical BILD 1633 SE significantly reduced the cutaneous lesions caused by both HSV-1 dlsptk and PAAr5 infections. The effect of BILD 1633 SE against HSV-1 PAAr5 infections was more prominent and was inoculum and dose dependent, with AUC reductions of 96 and 67% against infections with 106 and 107 PFU per inoculation site, respectively. BILD 1633 SE also significantly decreased the lesions caused by HSV-1dlsptk infection (28 to 51% AUC reduction). Combination therapy with topical BILD 1633 SE (5%) and ACV in drinking water (5 mg/ml) produced an antiviral effect against HSV-1 dlsptk and PAAr5 infections that was more than the sum of the effects of both drugs. This is the first report that a selective HSV RR subunit association inhibitor can be effective against ACV-resistant HSV infections in vivo.

scholarly journals Oral Bioavailability and In Vivo Efficacy of the Helicase-Primase Inhibitor BILS 45 BS against Acyclovir-Resistant Herpes Simplex Virus Type 1

2003 ◽  
Vol 47 (6) ◽  
pp. 1798-1804 ◽  
Author(s):  
Jianmin Duan ◽  
Michel Liuzzi ◽  
William Paris ◽  
Francine Liard ◽  
Abigail Browne ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nude Mice ◽  
Oral Bioavailability ◽  
Oral Treatment ◽  
Cutaneous Lesions ◽  
Mutant Strains ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT This study investigated the oral bioavailability and efficacy of BILS 45 BS, a selective herpes simplex virus (HSV) helicase-primase inhibitor, against acyclovir (ACV)-resistant (ACVr) infections mediated by the HSV type 1 (HSV-1) dlsptk and PAAr5 mutant strains. In vitro, the compound was more potent than ACV against wild-type clinical and laboratory HSV-1 strains and ACVr HSV isolates, as determined by a standard plaque reduction assay, with a mean 50% effective concentration of about 0.15 μM. The oral bioavailability of BILS 45 BS in hairless mice was 49%, with a peak concentration in plasma of 31.5 μM after administration of a single dose of 25 mg/kg. Following cutaneous infection of nude mice, both the HSV-1 dlsptk and PAAr5 mutant strains induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with ACV (100 or 125 mg/kg/day, three times a day by gavage) did not affect either mutant-induced infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by both ACVr HSV-1 mutants. The 50% effective doses of BILS 45 BS were 56.7 and 61 mg/kg/day against dlsptk- and PAAr5-induced infections, respectively. Taken together, our results demonstrate very effective oral therapy of experimental ACVr HSV-1 infections in nude mice and support the potential use of HSV helicase-primase inhibitors for the treatment of nucleoside-resistant HSV disease in humans.

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