Treatment of postherpetic neuralgia: a systematic review of the literature.

Alper BS, Lewis PR. Department of Family & Community Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65212, USA. alperb@health.missouri.edu

J Fam Pract 2002 Feb;51(2):121-8

OBJECTIVES: We wanted to determine whether any treatment had been shown to reduce pain or disability from postherpetic neuralgia (PHN), a common sequela of herpes zoster in elderly patients.

STUDY DESIGN: We undertook a systematic review of English-language randomized controlled trials (RCTs) of treatments of PHN with evaluation periods longer than 24 hours.

DATA SOURCES: We systematically searched

MEDLINE, Current Contents, and the Cochrane Library. We also searched reference lists of identified trials and reviews and contacted content experts.

OUTCOMES MEASURED: Two reviewers independently evaluated RCTs for methodologic quality and data extraction. Outcomes of primary focus were pain and quality of life.

RESULTS: Twenty-seven RCTs met inclusion criteria and were reviewed. Six trials of tricyclic antidepressants found evidence for clinically meaningful effects over 6 weeks. All other treatments were evaluated in no more than 2 trials meeting our inclusion criteria. Topical capsaicin 0.075%, gabapentin, and controlled-release oxycodone were shown to be effective, but the clinically meaningful benefit is difficult to quantify. Intrathecal methylprednisolone and possibly bupivacaine sympathetic blocks are helpful in refractory cases. Other treatments evaluated, including topical lidocaine, had no evidence or inconsistent evidence of benefit.

CONCLUSIONS: No single best treatment for PHN is known. Tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone are effective for alleviating PHN; however, long-term, clinically meaningful benefits are uncertain and side effects are common. Patients with PHN refractory to these therapies may benefit from intrathecal methylprednisolone. Little evidence is available regarding treatment of PHN of less than 6 months' duration.

An evaluation of the antioxidant and antiviral action of extracts of rosemary and Provencal herbs.

Aruoma OI, Spencer JP, Rossi R, Aeschbach R, Khan A, Mahmood N, Munoz A, Murcia A, Butler J, Halliwell B. Pharmacology Group, University of London King's College, UK.

Food Chem Toxicol 1996 May;34(5):449-56

Extracts of herbs and spices are increasingly of interest in the food industry because they retard oxidative degradation of lipids. There is also increasing interest in the antiviral activity of plant products. A liquid, deodorized rosemary extract and an oily extract of a mixture of Provencal herbs were tested for antioxidant and antiviral action in vitro. The rosemary extract (Herbor 025) and the extract of Provencal herbs (Spice Cocktail) inhibited peroxidation of phospholipid liposomes with 50% inhibition concentration values of 0.0009% (v/v) and 0.0035% (v/v), respectively. Herbor 025 and the spice cocktail (at 0.2%, v/v) reacted with trichloromethylperoxyl radical with calculated rates of 2.7 x 10(4) s-1 and 1.5 x 10(3) s-1, respectively. The main active components in the herbal preparations, carnosol and carnosic acid, at 0.05% (v/v) react with rate constants of (1-3) x 10(6) M-1 sec-1 and 2.7 x 10(7) M-1 sec-1, respectively. Both extracts show good antioxidant activity in the Rancimat test, especially in lard. Herbor 025 and the spice cocktail inhibited human immunodeficiency virus (HIV) infection at very low concentrations which were also cytotoxic. However, purified carnosol exhibited definite anti-HIV activity at a concentration (8 microM) which was not cytotoxic. Both preparations promoted some DNA damage in the copper-phenanthroline and the bleomycin-iron systems. The two herbal preparations possess antioxidant properties that may make them useful in the food matrix.

Capsaicin in the treatment of dermatologic disease.

Bernstein JE.

Cutis 1987 Apr;39(4):352-3

Capsaicin cream is the first of a class of neuropeptide active agents to be introduced into dermatologic therapy. Capsaicin's effects appear primarily related to its ability to deplete the neuropeptide substance P from local sensory terminals in the skin. The use of capsaicin cream in the treatment of postherpetic neuralgia and psoriasis is discussed. I believe that capsaicin and other neuropeptide active agents may become important therapeutic modalities for the dermatologist in the near future.

Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study.

Bernstein JE, Bickers DR, Dahl MV, Roshal JY.

J Am Acad Dermatol 1987 Jul;17(1):93-6

Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.

Topical capsaicin treatment of chronic postherpetic neuralgia.

Bernstein JE, Korman NJ, Bickers DR, Dahl MV, Millikan LE. Department of Clinical Research, GenDerm Corp., Northbrook, IL.

J Am Acad Dermatol 1989 Aug;21(2 Pt 1):265-70

Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.

Postherpetic neuralgia: role of gabapentin and other treatment modalities.

Beydoun A. Department of Neurology, University of Michigan Medical School, Ann Arbor 48109, USA.

Epilepsia 1999;40 Suppl 6:S51-6; discussion S73-4

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural gamma-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.

[Gabapentin therapy for pain] [Article in German]

Block F. Neurologische Klinik der RWTH Aachen. fblock@post.klinkum.rwth-aachen.de

Nervenarzt 2001 Feb;72(2):69-77

Gabapentin, which has been approved for add-on therapy of focal seizures, is increasingly used for treatment of neuropathic pain. Its analgesic effect is supposed to be due to reduction of glutamatergic transmission, improvement of GABAergic transmission and to binding to voltage-dependent calcium channels. Experimental studies demonstrated an ameliorating effect of gabapentin on neuropathic pain. Placebo-controlled studies revealed an efficacy of gabapentin against pain in diabetic neuropathy and postherpetic neuralgia and in prophylaxis of migraine. Case reports show an analgesic effect of gabapentin in trigeminus neuralgia and in reflex sympathetic dystrophy. The main adverse events are dizziness, ataxia and somnolence. Controlled studies, which compare the efficacy of gabapentin with that of the respective reference drug, are needed to evaluate its importance in treatment of pain.

Echinacea-induced cytokine production by human macrophages.

Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG. Nutri-Pro LC, Salt Lake City, Utah, USA.

Int J Immunopharmacol. 1997 Jul;19(7):371-9.

Echinacea purpurea, a plant originally used by native Americans to treat respiratory infections, was evaluated for its ability to stimulate the production of cytokines by normal human peripheral blood macrophages in vitro. Commercial preparations of echinacea fresh pressed juice and dried juice were tested at concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared to endotoxin stimulated and unstimulated controls. Cytokine production was measured by ELISA after 18 h of incubation for IL-1 and 36 and 72 h for TNF-alpha, IL-6, and IL-10. Macrophages cultured in concentrations of Echinacea as low as 0.012 microgram/ml produced significantly higher levels of IL-1, TNF-alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. The high levels of IL-1, TNF-alpha, and IL-10 induced by very low levels of echinacea are consistent with an immune activated antiviral effect. Echinacea induced lower levels of IL-6 in comparison to the other cytokines measured. These results demonstrate the immune stimulatory ability of the unpurified fresh pressed juice of Echinacea purpurea and offer some insight into the nature of the resulting immune response as compared to endotoxin.

Treatment of herpes zoster and postherpetic neuralgia.

Carmichael JK. University of Arizona College of Medicine, Tucson.

Am Fam Physician 1991 Jul;44(1):203-10

Herpes zoster results from reactivation of latent varicella-zoster virus. It is most common in elderly patients and immunosuppressed patients, especially those with human immunodeficiency virus (HIV) infection. Zoster is often the earliest indicator of HIV infection. The acute course of herpes zoster is generally benign, but systemic complications may be fatal. Postherpetic neuralgia is the major chronic complication and is a difficult management problem. High-dose acyclovir (800 mg orally five times daily) has recently been approved for treatment of herpes zoster and, if started early, decreases the duration and severity of symptoms. In the prevention of postherpetic neuralgia, acyclovir does not appear to be effective, and the efficacy of steroids is questionable. The best therapy currently available for postherpetic neuralgia is amitriptyline, topical capsaicin and transcutaneous electrical stimulation.

Effect of antimicrobial factors in human milk on rhinoviruses and milk-borne cytomegalovirus in vitro.

Clarke NM, May JT. Department of Microbiology, LaTrobe University, Bundoora, Victoria, Australia.

J Med Microbiol 2000 Aug;49(8):719-23

Various antimicrobial factors present in human milk were tested for in-vitro antiviral activity against three rhinoviruses (two clinical isolates and rhinovirus 2) and an isolate of cytomegalovirus (CMV) from human milk. These factors included the gangliosides GM1, 2 and 3, sialyl-lactose, chondroitin sulphates A, B and C, prostaglandins E2 and F2alpha, monolaurin, vitamin A and the protein lactoferrin. All were tested for their ability to inhibit growth of the viruses in cell culture. Human milk was also tested for antiviral activity against these viruses. Only vitamin A, monolaurin and lactoferrin inhibited the growth of CMV, whereas both prostaglandins enhanced the growth of this virus at least four-fold. CMV infects infants from milk but, nevertheless, the milk-borne CMV isolate showed no special resistance to any of the antiviral factors tested. None of the compounds inhibited or enhanced the growth of the rhinoviruses. However, human milk decreased the growth of some of the rhinoviruses and specific secretory immunoglobulin A (sIgA) neutralised the virus.

Inhibition of tumour growth and inflammation by consumption of tea.

Das M, Sur P, Gomes A, Vedasiromoni JR, Ganguly DK. Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta 700 032, India.

Phytother Res 2002 Mar;16 Suppl 1:S40-4

The antitumour effect of tea was evaluated in the 3-methylcholanthrene (3-MC) induced solid tumour model in mice. Both black and green tea inhibited tumour growth and prevented metastasis. Histopathological study showed that tea treatment was able to reduce malignancy. Superoxide dismutase (SOD), a free radical scavenger, was found to be significantly increased in the serum of mice administered tea. Moreover, tea extracts were able to reduce the level of thiobarbituric acid reactive substance (TBARS) in the sera of mice. Tea extracts (both black and green) also showed antiinflammatory activity in the carrageenan-induced paw oedema model in the rat. Copyright 2002 John Wiley & Sons, Ltd.

Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea as a candidate anti-HIV agent.

Fassina G, Buffa A, Benelli R, Varnier OE, Noonan DM, Albini A. Instituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.

AIDS 2002 Apr 12;16(6):939-41

Epigallocatechin-3-gallate (EGCG), one of the components of green tea, has been suggested to have antiviral activity. To determine the effects of EGCG on HIV infection, peripheral blood lymphocytes were incubated with either LAI/IIIB or Bal HIV strains and increasing concentrations of EGCG. EGCG strongly inhibited the replication of both virus strains as determined by reverse transcriptase and p24 assays on the cell supernatants.

Demonstration of the anti-viral activity of garlic extract against human cytomegalovirus in vitro.

Guo NL, Lu DP, Woods GL, Reed E, Zhou GZ, Zhang LB, Waldman RH. Institute of Hematology, Beijing Medical University.

Chin Med J (Engl) 1993 Feb;106(2):93-6

The in vitro anti-viral activity of garlic extract (GE) on human cytomegalovirus (HCMV) was evaluated by tissue culture, plaque reduction and early antigen assay. A dose dependent inhibitory effect of GE was evident when GE was applied simultaneously with HCMV. But the effect was stronger when the monolayers were pretreated with GE. In addition, the anti-viral effect of GE persisted long in infected cells after its being removed from the culture medium. The strongest anti-viral effect of GE was demonstrated when it was applied continuously. It is therefore recommended that clinical use of GE against HCMV infection should be persistent and the prophylactic use of GE is preferable in immunocompromised patients.

Herpes zoster: treatment with cimetidine.

Hayne ST, Mercer JB.

Can Med Assoc J 1983 Dec 15;129(12):1284-5

The active phase of herpes zoster can be predicted from the length of time it takes for all the vesicles to erupt. A case is reported in which cimetidine therapy appeared to reduce the expected length of the active phase from 35 days or longer to 10 days.

Effect of Ganoderma lucidum on postherpetic neuralgia.

Hijikata Y, Yamada S. Tokyo Hijikata Clinic, Osaka, Japan.

Am J Chin Med. 1998;26(3-4):375-81.

Administration of hot water soluble extracts of Ganoderma lucidum (GI) (36 to 72 g dry weight/day) decreased pain dramatically in two patients with postherpetic neuralgia recalcitrant to standard therapy and two other patients with severe pain due to herpes zoster infection.

Dietary polyunsaturated fatty acids and inflammatory mediator production.

James MJ, Gibson RA, Cleland LG. Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the Department of Pediatrics and Child Health, Flinders Medical Center, Bedford Park, Australia.

Am J Clin Nutr 2000 Jan;71(1 Suppl):343S-8S

Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.

[Efficacy of cimetidine in treatment of Herpes zoster in the first 5 days from the moment of disease manifestation] [Article in Polish]

Kapinska-Mrowiecka M, Turowski G.

Pol Tyg Lek 1996 Jun;51(23-26):338-9

221 patients with Herpes zoster have undergone the treatment. They were given cimetidine in the daily dose 3 x 200 mg and 1 x 400 mg to night. It was proved that the efficacy of the Herpes zoster treatment by cimetidine is inversely proportional to the time of the disease duration. The authors suggest to use cimetidine in the treatment of Herpes zoster virus infections even during the prodromal period.

IN vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine.

Komlos L, Notmann J, Arieli J, Hart J, Levinsky H, Halbrecht I, Sendovsky U. B Gattegno Research Institute for Human Reproduction and Fetal Development, Hasharon Hospital, Golda Medical Center, Petah-Tiqva, Israel.

Asian Pac J Allergy Immunol 1994 Jun;12(1):51-8

In a double-blind placebo-control study the immunomodulating effect of cimetidine treatment for one week and placebo was investigated for cell-mediated immune reactions of 22 patients with herpes zoster (HZ). The mitogen induced leukocyte migration inhibition test (LMIT) and the in vitro proliferation of the patients' lymphocytes to exogenous IL-2 were used. Before any treatment, the mitogen induced leukocyte migration inhibition capacity (LMIC) of HZ patients was found to be significantly reduced (p < 0.02) as compared to healthy blood bank donors (controls). After one week, within the same treatment, the LMIC was significantly improved (p < 0.01). The patients' lymphoproliferative response to IL-2, before any treatment, was not significantly different from that of controls (p < 0.05). However, significantly higher values (p < 0.001) were found in patients tested 7 days after the disease onset as compared to those tested after 12 days. One-week cimetidine treatment significantly improved (p < 0.05) the lymphoproliferative response to IL-2 of initially low responders and had no effect on higher responder patients. In contrast to this, after one week of placebo treatment, a significant decrease in the patients' lymphoproliferative response to IL-2 could be observed as compared to patients' initial responses (p < 0.05) or to those of controls (p < 0.05). Although the number of cases is very small. The data suggest that after cimetidine treatment, as compared to placebo, healing from skin rash and pain was achieved in a significantly shorter time (p <0.01).

Development and evaluation of microbicidal hydrogels containing monoglyceride as the active ingredient.

Kristmundsdottir T, Arnadottir SG, Bergsson G, Thormar H. Department of Pharmacy and Institute of Biology, University of Iceland, Reykjavik, Iceland. thordisk@hi.is

J Pharm Sci 1999 Oct;88(10):1011-5

A number of medium-chain saturated and long-chain unsaturated fatty acids and their monoglycerides were tested against herpes simplex virus (HSV-1) to determine which lipids were most active during a short incubation time. The aim was to find which lipid would be preferable as the active ingredient in a virucidal hydrogel formulation for the purpose of preventing transmission of pathogens to mucosal membranes, particularly sexually transmitted viruses, such as herpes simplex virus and human immunodeficiency virus (HIV), and bacteria, such as Chlamydia trachomatis and Neisseria gonorrheae. The main strategy was that the formulations would be fast-acting, killing large numbers of virus or bacteria on contact in a short time, preferably causing at least a 10000-fold reduction in virus/bacteria titer in 1-5 min. Monocaprin, the 1-monoglyceride of capric acid, and lauric acid were found to be most active of all the lipids tested, causing a greater than 100000-fold reduction in virus titer in 1 min at a concentration of 20 mM. When tested at a concentration of 10 mM for 1 min, monocaprin was still fully active whereas lauric acid had no or negligible activity. It was concluded that monocaprin was most suitable as the active ingredient in a fast-acting virucidal gel formulation, and several hydrogel formulations containing monocaprin were tested. Formulations where the monoglyceride was dissolved in glycofurol were found to be active against HSV-1. The hydrogel formulations containing 20 mM monocaprin were highly virucidal in vitro and caused a greater than 100000-fold (HSV-1) inactivation of virus in human semen in 1 min. Formulations in dilution 1:10 were cytotoxic in monolayers of CV-1 cells, but they were 10-100 fold less cytotoxic than a commercial product which contains 2% nonoxynol-9.

Cimetidine: an immunomodulator.

Kumar A. Department of Pediatrics and Human Development, Michigan State University, East Lansing 48824.

DICP 1990 Mar;24(3):289-95

Suppressor T lymphocytes possess histamine2 (H2) receptors and contribute significantly to the function of the immune system. Experimentally, cimetidine, an H2-receptor antagonist, has been shown to enhance a variety of immunologic functions both in vivo and in vitro because of its inhibitory effects on suppressor-cell function. Successful tumor immunotherapy, as well as some protection from infection, has been reported in experimental animals. Patients receiving cimetidine have been shown to exhibit enhanced cell-mediated immunity as evaluated by increased response to skin-test antigens, restoration of sensitivity following development of acquired tolerance, and increased responses of lymphocytes to mitogen stimulation. Preliminary reports also indicate that cimetidine may offer therapeutic benefits for patients with Varicella zoster and Herpes simplex infections, as well as those suffering from mucocutaneous candidiasis and common variable hypogammaglobulinemia. These immunoregulatory effects are dose-related but are not always consistent. Because of its inhibitory effect on suppressor function, cimetidine treatment may be deleterious in patients with organ transplant and autoimmune disorders. Cimetidine should be used as an immunomodulator on an experimental basis only.

In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents.

Ma SC, He ZD, Deng XL, But PP, Ooi VE, Xu HX, Lee SH, Lee SF. Department of Biology and Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin.

Chem Pharm Bull (Tokyo) 2001 Nov;49(11):1471-3

Six secoiridoid glucosides, lucidumoside C (1), oleoside dimethylester (2), neonuezhenide (3), oleuropein (4), ligustroside (5) and lucidumoside A (6), isolated from the fruits of Ligustrum lucidum (Oleaceae), were examined in vitro for their activities against four strains of pathogenic viruses, namely herpes simplex type I virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). Antiviral activities were evaluated by the cytopathic effect (CPE) inhibitory assay. The purpose was to check if the antioxidative potency of these glucosides correlated with their antiviral potency. Results showed that none of the glucosides had any significant activity against HSV-1 and Flu A. Oleuropein, however, showed significant antiviral activities against RSV and Para 3 with IC50 value of 23.4 and 11.7 microg/ml, respectively. Lucidumoside C, oleoside dimethylester and ligustroside showed potent or moderate antiviral activities against Para 3 with IC50 values of 15.6-20.8 microg/ml. These results also documented that the anti-oxidative potency of these secoiriodoid glucosides was not directly related to their antiviral effects.

Cimetidine as an immunomodulator in the treatment of herpes zoster.

Miller A, Harel D, Laor A, Lahat N. Department of Neurology, Lady Davis Carmel Hospital, Haifa, Israel.

J Neuroimmunol 1989 Mar;22(1):69-76

As there is evidence of a possible immunoregulatory role for H2-histamine receptor antagonists, we carried out a prospective randomized trial to evaluate the in vivo and in vitro effect of cimetidine, an H2-blocker, in the treatment of herpes zoster infection. Cimetidine treatment shortened the median interval until the first decrease in pain, the median interval until the complete resolution of pain and promoted faster complete healing of skin lesions than symptomatic treatment. The immunological trends observed in vitro support an important role for histamine in the induction of immunosuppression, as measured by the response to the mitogen phytohemagglutinin. This effect of histamine was antagonized by cimetidine.

Inhibitory effect of carnosic acid on HIV-1 protease in cell-free assays [corrected]

Paris A, Strukelj B, Renko M, Turk V, Pukl M, Umek A, Korant BD. Department of Biochemistry, Jozef Stefan Institute, Ljubljana, Slovenia.

J Nat Prod 1993 Aug;56(8):1426-30

In order to find new effective HIV protease inhibitors, two diterpenes (carnosic acid [1] and carnosol [5]) were isolated from rosemary (Rosmarinus officinalis L.), and rosmanol [2] and semisynthetic derivatives (7-O-methylrosmanol [3], 7-O-ethylrosmanol [4], and 11,12-O,O-dimethylcarnosol [6]) were prepared. The inhibitory activity of all six compounds against HIV-1 protease was tested. The carnosic acid [1] showed the strongest inhibitory effect (IC90 = 0.08 micrograms/ml). The same compound was also assayed against HIV-1 virus replication (IC90 = 0.32 micrograms/ml). The cytotoxic TC90 on H9 lymphocytes was 0.36 micrograms/ml, which is very close to the effective antiviral dose. Additionally, the tested compounds did not inhibit cellular aspartic proteases cathepsin D and pepsin at the concentration range up to 10 micrograms/ml [corrected].

Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.

Peikert A, Hentrich M, Ochs G. Neurologische Klinik und Poliklinik, Technischen Universitat, Munchen, Federal Republic of Germany.

J Neurol 1991 Dec;238(8):452-6

In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.

Capsaicin evoked pain and allodynia in post-herpetic neuralgia.

Petersen KL, Fields HL, Brennum J, Sandroni P, Rowbotham MC. Department of Neurology, UCSF Pain Clinical Research Center, University of California, San Francisco, 94115, USA. klp@itsa.ucsf.edu

Pain 2000 Nov;88(2):125-33

The hypothesis that the pain and allodynia associated with post-herpetic neuralgia (PHN) is maintained by a combination of input from preserved primary afferent nociceptors and sensitization of central pain transmitting neurons was examined in 17 subjects with PHN. Pain, allodynia, thermal sensory function, cutaneous innervation, and response to controlled application of 0.075% capsaicin were measured. Compared to mirror-image skin, applying capsaicin on a 9 cm(2) area of PHN skin significantly increased overall PHN pain and allodynia in 11 of 17 subjects. These 'capsaicin responders' were characterized by higher average daily pain, higher allodynia ratings, and relatively preserved sensory function at baseline compared to the non-responders. In three of the 'capsaicin responders' the area of allodynia expanded into previously non-allodynic and non-painful skin that had normal sensory function and cutaneous innervation. These observations support the hypothesis that allodynia in some PHN patients is a form of chronic secondary hyperalgesia maintained by input from intact and possibly 'irritable' primary afferent nociceptors to a sensitized CNS.

Anti-inflammatory properties of docosahexaenoic and eicosapentaenoic acids in phorbol-ester-induced mouse ear inflammation.

Raederstorff D, Pantze M, Bachmann H, Moser U. Department of Vitamin and Nutrition Research, F.Hoffmann-La Roche Ltd, Basel, Switzerland.

Int Arch Allergy Immunol 1996 Nov;111(3):284-90

Laboratory animal models and clinical studies suggest that dietary n-3 fatty acids are beneficial in diseases with an inflammatory component such as rheumatoid arthritis or psoriasis. In the present study we investigated the effect of purified docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on phorbol ester (TPA)-induced acute inflammation. Mice were fed for 6 weeks a diet containing 5% corn oil enriched with either 1% DHA or 1% EPA and compared with a group receiving 6% corn oil only. The dietary treatment with DHA or EPA elevated the n-3 polyunsaturated fatty acids as expected in the spleen and ear phospholipids, associated with a reduction in arachidonic acid levels. The degree of ear inflammation was quantified by measuring the four parameters including (1) edema as the increase in ear biopsy weight, (2) polymorphonuclear cell infiltration as myeloperoxidase activity (MPO) at the site of inflammation, (3) prostaglandin E2 (PGE2) and (4) leukotriene B4 (LTB4) concentrations in ear edema. The addition of DHA to the diet reduced significantly the edema formation and the MPO activity 24 h after TPA challenge. Both DHA and EPA significantly reduced the PGE2 and LTB4 levels compared with animals fed corn oil. This result suggests that DHA rather than EPA may be useful in the adjuvant treatment of diseases where acute inflammatory processes play a role.

Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study.

Rice AS, Maton S; Postherpetic Neuralgia Study Group. Pain Research Group, Department of Anaesthetics, Imperial College School of Medicine, Chelsea and Westminster Hospital Campus, 369 Fulham Road, London SW10 9NH, UK. a.rice@ic.ac.uk

Pain 2001 Nov;94(2):215-24

A multicentre double blind, randomised, placebo controlled 7-week study evaluated the efficacy and safety of gabapentin 1800 or 2400 mg/day in treating postherpetic neuralgia. Three hundred and thirty-four men and women aged at least 18 years (mean 73) received gabapentin 1800 or 2400 mg daily or placebo in three divided doses with a forced titration schedule. The primary outcome measure was change in average daily pain diary score (baseline week v final week). Secondary outcomes included mean weekly sleep interference score; Short Form-McGill Pain Questionnaire (SF-MPQ); Clinician and Patient Global Impression of Change (CGIC/PGIC); Short Form-36 Health Survey (SF-36). From week 1, pain scores showed a significantly greater improvement with gabapentin: the final difference v baseline was -34.5% for the 1800 mg dose, -34.4% for the 2400 mg dose compared with -15.7% for the placebo group. The difference vs. placebo was 18.8% for the 1800 mg dose (95% confidence interval 10.9-26.8%; P<0.01) and 18.7% for the 2400 mg dose (10.7-26.7%; P<0.01). Sleep interference diaries showed a similar pattern. There were significant differences in favour of gabapentin for number of patients reporting >50% reduction in their pain intensity, in the CGIC and PGIC, in the sensory and total scores of the SF-MPQ (both doses), in the visual analogue scale of pain of the SF-MPQ (2400 mg only) and in the vitality, bodily pain and mental health domains of the SF-36. Overall gabapentin was well tolerated. The most common adverse events were dizziness and somnolence, particularly during the titration phase. Thus, this study confirms the role of gabapentin as an efficacious and well-tolerated treatment for postherpetic neuralgia.

Treatment of post herpetic neuralgia in the elderly.

Robertson DR, George CF. Geriatric Medicine, Southampton General Hospital, UK.

Br Med Bull 1990 Jan;46(1):113-23

The incidence of acute herpes zoster and post herpetic neuralgia (PHN) increases with age. PHN resolves spontaneously within three months in approximately 50% of cases, although 22% experience discomfort for more than a year. There is little good evidence that treatment with antiviral agents, corticosteroids, local and regional anaesthesia, amantadine or levodopa in the acute stage can prevent the development of PHN. However, few studies have sufficient statistical power to allow firm conclusions to be drawn. Amitriptyline is beneficial in patients with established PHN and has an analgesic effect which is independent of its antidepressant action. Anticonvulsants and neuroleptics are of unproven efficacy and should be avoided in the elderly as side effects are common. Various local anaesthetic and surgical techniques may provide temporary relief in individual patients although none has been shown to produce consistent benefit. Transcutaneous electrical nerve stimulation (TENS) is free from adverse effects and appears to benefit some patients. Intractable pain often results in over-prescribing with the risk of adverse drug reactions. Drug therapy should be minimized with careful assessment of the risk/benefit ratio for any additional medication.

Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia.

Rowbotham MC, Reisner-Keller LA, Fields HL. Department of Neurology, University of California, San Francisco 94143.

Neurology 1991 Jul;41(7):1024-8

We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session, randomized, double-blind, placebo-controlled trial. Compared with saline placebo, both lidocaine and morphine reduced pain intensity. Reductions in pain did not correlate with side effects produced by the infusions. For morphine, there was a significant correlation between reductions in pain intensity and blood level achieved. In the majority of subjects who reported definite pain relief, allodynia also disappeared. The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs.

[The inhibitory effects of catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and DNA polymerases] [Article in Chinese]

Tao P. Institute of Medical Biotechnology, Beijing.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1992 Oct;14(5):334-8

Catechin derivatives including (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and green tea extract (GTE) were found to inhibit the activities of cloned human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), duck hepatitis B virus replication complexes reverse transcriptase (DHBV RCs RT), herpes simplex virus 1 DNA polymerase (HSV-1 DNAP) and cow thymus DNA polymerase alpha (CT DNAP alpha). EGCG and ECG were shown to be very potent inhibitors of HIV-1 RT. According to the IC50 values for HIV-1 RT, these compounds can be ordered as EGCG 0.0066 mumol/L > ECG 0.084 mumol/L > GTE 0.1 microgram/ml > EGC 7.2 mumol/L. DHBV RCs RT was the least sensitive to these compounds. Kinetic study showed that EGCG exerts a mixed inhibition with respect to external template inducer poly (rA).oligo (dT) 12-18 and a noncompetitive inhibition with respect to substrate dTTP for HIV-1 RT. Bovine serum albumin significantly reduced the inhibitory effects of catechin analogues and GTE on HIV-1 RT. In tissue culture GTE inhibited the cytopathic effect of coxsackie B3 virus, but did not inhibit the cytopathic effects of HSV-1, HSV-2, influenza A or influenza B viruses.

Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults.

Thies F, Miles EA, Nebe-von-Caron G, Powell JR, Hurst TL, Newsholme EA, Calder PC. Department of Biochemistry, University of Oxford, United Kingdom.

Lipids 2001 Nov;36(11):1183-93

Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.

Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus.

Thompson KD. Department of Pathology, The University of Chicago Medical Center, IL 60637, USA. thompson@midway.uchicago.edu

Antiviral Res 1998 Jul;39(1):55-61

Viracea, a topical microbicide, is a blend of benzalkonium chloride and phytochemicals derived from Echinacea purpurea and is a proprietary formula from Destiny BioMediX Corp. Viracea was tested against 40 strains of herpes simplex virus (HSV): 15 strains (five HSV-1 and ten HSV-2) were resistant to acyclovir (ACV-R) and 25 strains (13 HSV-1 and 12 HSV-2) were susceptible to ACV (ACV-S). The median ED50 of Viracea for the five ACV-R strains of HSV-1 was a 1:100 dilution of the drug with a range of 1:50-1:400. The median ED50 of Viracea for the ten ACV-R strains of HSV-2 was 1:200 with a range of 1:50-1:3200. For the ACV-S strains of HSV-1 and HSV-2, the median ED50 of Viracea was 1:100 and 1:200, respectively. The cytotoxicity of Viracea was evaluated in a standard neutral red dye uptake assay in human foreskin fibroblasts. The cytotoxicity of Viracea approached only 50% at the highest concentration of the drug tested, a 1:2 dilution, indicating that Viracea is non-toxic in this cell cytotoxicity assay. Although the active component(s) in Viracea that has anti-HSV activity is not known, it appears that this extract has good antiviral activity against both ACV resistant and ACV susceptible strains of HSV-1 and HSV-2.

Cimetidine in the treatment of herpesvirus infections.

van der Spuy S, Levy DW, Levin W.

S Afr Med J 1980 Jul 19;58(3):112-6

In August 1977 a patient developed herpes zoster just before she commenced a course of cimetidine (Tagamet; Smith, Kline & French) for a chronic gastric ulcer. She experienced both rapid relief of the ulcer symptoms and, rather unexpectedly, dramatic relief of the herpetic pain and rapid disappearance of the eruption. On the basis of this observation cimetidine was prescribed to 21 patients with herpes zoster. The results continued to be encouraging in all but 3 patients. The trial was therefore extended to other herpesvirus infections. In all but 1 of 7 patients with herpes labialis the blisters were aborted, and in 1 patient with herpes keratitis the result was also encouraging, the attacks being markedly shortened in duration and reduced in frequency. The results of this preliminary trial warrant a systematic scientific inquiry into the potential role of cimetidine in the treatment of hypesvirus infection, as well as a study of the mechanisms involved.

Post-herpetic neuralgia and topical capsaicin.

Watson CP, Evans RJ, Watt VR. Smythe Pain Clinic, Toronto General Hospital, University of Toronto, Ont., Canada.

Pain 1988 Jun;33(3):333-40

Topical 0.025% capsaicin was used to treat 33 patients with post-herpetic neuralgia (PHN). Thirty-nine percent of those entering the trial achieved at least a good result and 55% were improved or better. Fifty-six percent of the 23 patients completing the study had good or excellent pain relief after 4 weeks. Seventy-eight percent of the 23 noted at least some improvement in pain. Post-capsaicin burning was a common, untoward effect in most patients and in about one-third was so unbearable that the trial was terminated prematurely. This treatment appears to be a useful modality in PHN, particularly in the elderly in whom oral medications are often poorly tolerated; however, it does require supervision. A double-blind, controlled trial is now necessary.

In vitro virucidal effects of Allium sativum (garlic) extract and compounds.

Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG. Department of Microbiology, Brigham Young University, Provo, Utah 84602.

Planta Med 1992 Oct;58(5):417-23

Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG, Schleupner CJ, Hayden F, Wolf J, Soong SJ. Department of Pediatrics, University of Alabama at Birmingham, Children's Hospital 35233, USA.

Ann Intern Med 1996 Sep 1;125(5):376-83

OBJECTIVE: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes.

DESIGN: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design.

SETTING: 15 university hospitals or affilliated clinics.

PATIENTS: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment.

INTERVENTION: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone.

MEASUREMENTS: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinical visit. An intention-to-treat analysis was used.

RESULTS: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group.

CONCLUSIONS: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life.

Herpes zoster as a sign of AIDS-related complex.

Wilkerson MG, Jordan WP, Kerkering TM. Medical College of Virginia, Richmond.

Am Fam Physician 1987 Oct;36(4):233-5

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster.

Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks J. Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, United Kingdom.

N Engl J Med 1994 Mar 31;330(13):896-900

BACKGROUND. Acyclovir given for 7 to 10 days is of proved benefit in acute herpes zoster, but studies of its effectiveness in preventing postherpetic neuralgia have had conflicting results. The role of corticosteroids in the treatment of herpes zoster is also controversial.

METHODS. We conducted a double-blind, controlled trial in patients with acute herpes zoster to determine whether either 21 days of acyclovir therapy or the addition of prednisolone offered any improvement over 7 days of acyclovir therapy. Patients with a rash of less than 72 hours' duration were assigned to receive acyclovir (800 mg orally, five times daily) for 7 days with either prednisolone or placebo, or acyclovir for 21 days with either prednisolone or placebo. Prednisolone therapy was initiated at a dose of 40 mg per day and tapered over a three-week period. Patients were assessed frequently through day 28 and then monthly through month 6 to assess postherpetic neuralgia.

RESULTS. Of 400 patients recruited, 349 completed the study. No significant differences were detected between the four groups in the progression of the rash (P > 0.1). With steroid therapy, a significantly higher proportion of the rash area had healed on days 7 and 14 (P = 0.02). Pain reduction was greater during the acute phase of disease in patients treated with steroids or 21 days of acyclovir (P < 0.01 and P = 0.02, respectively, on day 7; P < 0.01 for steroid therapy on day 14). However, on follow-up there were no significant differences between any of the groups in the time to a first or a complete cessation of pain. The steroid recipients reported more adverse events.

CONCLUSIONS. In acute herpes zoster, treatment with acyclovir for 21 days or the addition of prednisolone to acyclovir therapy confers only slight benefits over standard 7-day treatment with acyclovir. Neither additional treatment reduces the frequency of postherpetic neuralgia.

[The treatment of zoster neuralgia] [Article in German]

Wulf H, Maier C, Schele HA. Klinik fur Anaesthesiologie und operative Intensivmedizin, Kiel.

Anaesthesist 1991 Oct;40(10):523-9

Neuralgic pain during or following herpes zoster infection is a common problem in pain therapy. The current management of neuralgias due to zoster is discussed with reference to patients in a chronic pain clinic within an anesthesiology department. The courses of 80 patients followed up for at least 3 months from the pain clinic at the University Hospital in Kiel were analyzed. The mean age was 69 years. The predominant locations for zoster lesions were the thoracic segments (65%) and the first branch of the trigeminal nerve (19%). Diabetes mellitus was present in 20% of the patients and malignant disease in 18%. In 2 patients recurrent postherpetic neuralgia was the first symptom of HIV infection. Despite pretreatment, the mean initial pain score was 8 on an analog scale (range 0-10). Acute herpes zoster pain during the infection was treated with virustatic agents, corticosteroids and sympathetic blocks. Postherpetic neuralgias required a more sophisticated approach, depending on the stage of the disease and the type of pain involved: sympathetic blockade with local anesthetic agents or injections of very low dose opioids to sympathetic ganglia, transcutaneous electrical nerve stimulation, and antidepressants or anticonvulsants. The success of the therapy is correlated with the duration of pain. If the history of zoster pain was less than 1 month, the majority of patients showed good or excellent results. On the other hand, only one-third of patients with a history longer than 6 months had adequate pain relief. Therefore, early and appropriate treatment is desirable for patients suffering from zoster neuralgias.

Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama.

Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M

J Altern Complement Med 1995 Winter;1(4):361-9

A standardized elderberry extract, Sambucol (SAM), reduced hemagglutination and inhibited replication of human influenza viruses type A/Shangdong 9/93 (H3N2), A/Beijing 32/92 (H3N2), A/Texas 36/91 (H1N1), A/Singapore 6/86 (H1N1), type B/Panama 45/90, B/Yamagata 16/88, B/Ann Arbor 1/86, and of animal strains from Northern European swine and turkeys, A/Sw/Ger 2/81, A/Tur/Ger 3/91, and A/Sw/Ger 8533/91 in Madin-Darby canine kidney cells. A placebo-controlled, double blind study was carried out on a group of individuals living in an agricultural community (kibbutz) during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. Sera obtained in the acute and convalescent phases were tested for the presence of antibodies to influenza A, B, respiratory syncytial, and adenoviruses. Convalescent phase serologies showed higher mean and mean geometric hemagglutination inhibition (HI) titers to influenza B in the group treated with SAM than in the control group. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM-treated group within 2 days, whereas in the control group 91.7% of the patients showed an improvement within 6 days (p < 0.001). A complete cure was achieved within 2 to 3 days in nearly 90% of the SAM-treated group and within at least 6 days in the placebo group (p < 0.001). No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low cost, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B.

Clinical experiences using the antiviral 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) in Mexico.

Zertuche HF, Perches RD.

Ann N Y Acad Sci 1977 Mar 4;284:284-8

Follow-up of the use of ribavirin in 390 human patients in Mexico indicates the drug has been used to treat a variety of virus infections. No toxic manifestations of the drug were reported, and the subjective results suggest possible antiviral efficacy. A double-blind, placebo-controlled study using topically applied 5% ribavirin in ointment base against herpes zoster in cancer patients indicates definite efficacy against this specific disease.