A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain.
We report the result of a randomized, controlled, open trial of anti-thrombin therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients within 8 days after the onset of skin lesion were enrolled in the trial. Patients were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with or without intravenous administration of a specific anti-thrombin agent, argatroban (10 mg/day, three times a week). Administration of argatroban reduced pain intensity at the 4th through 21st day after the initiation of treatment as determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also shortened the median time to cessation of analgesic use (14 days vs. 24 days, p = 0.02, logrank test), although it did not significantly reduce the median time to cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the enrolled patients showed evidence of adverse effects including hemorrhagic diathesis. The results suggested that relatively low doses of argatroban are effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin expression by the vascular endothelial and sweat gland epithelial cells in the active skin lesion and transient elevation of plasma thrombin-antithrombin III complex levels in a proportion of patients suggest a lesional generation of thrombin in herpes zoster. This may be relevant to the beneficial effects of the anti-thrombin treatment on the resolution of herpes zoster-associated pain.
Fujii
K
K
Department of Dermatology, Kobe City General Hospital, Minatojima-Nakamachi, 4-6, Kobe 650-0046, Japan.
Kanno
Y
Y
Konishi
K
K
Ohgou
N
N
D000368:Aged; D000990:Antithrombin III; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D005260:Female; D006562:Herpes Zoster / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement; D010447:Peptide Hydrolases / Q000097:blood; D010875:Pipecolic Acids / Q000627:therapeutic use*; D011446:Prospective Studies; D011516:Prothrombin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013449:Sulfonamides; D016896:Treatment Outcome; D015854:Up-Regulation
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D011516:Prothrombin; D001120:Arginine; D010447:Peptide Hydrolases; C031942:argatroban