Postherpetic Neuralgia

Treatment of Postherpetic Neuralgia
JMAJ 47(11): 529–536, 2004

Akira OZAWA
Professor and Chairman, Dermatology, Course of Specialized Clinical Science,
Tokai University School of Medicine

Abstract: Herpes zoster, a commonly seen condition in daily medical practice, is
reported to occur in 10–20% of the population at some time during the lifespan.
Chronic, intractable postherpetic neuralgia, a sequela of herpes zoster, presents a
clinical challenge. In recent years, effective antiviral agents that can be used in the
outpatient setting have been developed for the treatment of herpes zoster and have
achieved good clinical efficacy. However, in the absence of any clear, decisive
treatment for postherpetic neuralgia, a variety of therapies have been elaborated
for use in clinical practice. This paper outlines the treatment of postherpetic
neuralgia and introduces therapeutic iontophoresis, which we have been using
with success in the clinical setting. The prevention and prediction of postherpetic
neuralgia is also discussed.
Key words:

Herpes zoster; Postherpetic neuralgia (PHN); Antiviral agents;
Iontophoresis therapy

of individuals affected is as high as 20 mill
ion.
Herpes zoster, a commonly occurring co Although herpes zoster is not lifethreatening,
ndition, is frequently encountered in the
dermatology clinic and various other clinics. I
t is
reported that the annual number of patie
nts
is 140–180 per 100,000 population and
that
10–20% of the population suffers from this d
isease at some time during the lifespan. In Jap
an,
approximately 500,000 people are affected
by
herpes zoster each year, and the total num
ber

Introduction

people a nt ged of eruptions. Antidepressants Tricyclic Clomipramine (25 Others Others including amitriptyline (30 150mg/day) imipramine.. 6 Indomethacin and others Although this preparation is used widely because it is easy to apply. 2003.000 ml of chloroform is applied topically 2 3 times weekly. and others Drug Therapy ● Systemic therapy Nonsteroidal anti-inflammatory drugs Usual oral dose. Keisi-ka-zyutsubuto. particularly at This article is a revised English version of a paper originally published in the Journal of the Japan Medical Association (Vol. 11 A. characteristics. 1) every patient with herpes zoster. acyclovir. pages 1259–1264). antiparkinson drugs (L-DOPA). 129. JMAJ. 47. No. incidence increases with age. PHN naturally does not occur i 65 years or older already number 23 mill n ion. The effect lasted for 3 hours. 70 80% improvement (in 1 case) Toki-sigyaku-ka-gosyuyu-shokyoto Effective in 5 out of 12 cases Antiarrhythmic drugs Mexiletine hydrochloride Alleviation in 10 out of 11 cases Others Antiviral agents (vidarabine. Alleviation in 5 out of 10 patients receiving 5 treatments 60 2% aspirin ointment. 8. processed Japanese aconite daughter root powder. 1 5 g 4 50 10 units/kg/day Effective in 10 out of 12 cases. 2002. ● Topical therapy Nonsteroidal Aspirin anti-inflammatory drugs Others 20ml of a solution prepared by dissolving 50g of aspirin in 1. its efficacy is variable. care must be taken so as not to continue oral widely used. which follows the successful treatme among those in their 80s. but there is a tendency to rule out their efficacy for PHN itself). No. ODT after application of 15 g Alleviation in 5 cases. The incide alnce gia as a manifestation of the disease of PHN is about 5% among patients and with chronic persistent postherpetic neural herpes zoster in their 60s. adverse effects. The Japanese text is a transcript of a lecture originally aired on December 2. November 2004—Vol. immunoglobulin (intravenous infusion at high doses). Ltd. with side effects in 4 Little efficacy. in its regular program “Special Course in Medicine”. Suppositories are poor. 5g. Care must also be taken because these drugs cause various side effects when doses orally. with side effects that pose problems Patients more than 6 months after onset of herpes zoster are amenable. Care must be taken not to continue therapy if there has been no response for 4 weeks.. OZAWA Table 1 Treatments of Postherpetic Neuralgia in Japan Therapeutic modality Dosage Efficacy. and others have been reported to be effective in preventing the development of PHN. vitamin B12. 529 . treatment for too long. although i accounting for 18% of the total populati ts on. The incidence of PHN and the duration of neuralgia were reduced. by the Nihon Sho rtwave Broadcasting Co. reaching about 1 gia 0% (PHN). In Japan. The dose is increased or decreased Because the effectiveness of prolonged treatment is depending on symptoms. and nortriptyline (10 30mg/day) Carbamazepine (an antiepileptic agent) 75mg/day) Extract of inflammatory rabbit skin inoculated with vaccinia virus Neurotropin (__units/day divided into one morning and one evening dose) Interferon 4 Chinese medicines (combined with nerve blocks) Herbal extracts.it poses the clinical problems of severe neur about 60 years of age and above.

Injection of 0. the efficacy decreases as the duration increases. forms of therapy are ineffective and in patients The treatment is administered at intervals of 2 6 having underlying diseases. As a rule.025% capsaicin cream. The procedure A weak electric current is applied through the pad is not painful. 5 times daily 10% lidocaine cream (to be applied 3 5 times daily) Alleviation in 5 of 10 patients receiving 5 treatments Lidocaine tape (containing 60% lidocaine) Effective for 12 hours 60 Nitrates (Isosorbide dinitrate is problematic because it causes headache. Symptomatic improvement achieved in 8 out of 10 cases. dibucaine and benzocain. more than 100 times. Efficacy rate: 36%. adverse effects.). Effective in 96% if of about ten times administered within 2 weeks after the onset. and if necessary. 47. but produced combination with steroids. It is less painful for the patient. November 2004—Vol.7 times). It may cause complications. Application causes a burning sensation. Capsaicin cataplasms. With PHN lasting for more than 1 month. camphor and sodium salicylate. Intravenous infusion Infusion of 0. 11 TREATMENT O F P O S T H E R P E T I C NEURALGIA (PHN ) Table 1 Treatments of Postherpetic Neuralgia in Japan (continued) Therapeutic modality Dosage Efficacy. but not in all cases The effect is transient. The procedure is simple. In some cases. 1 14 times (mean: 5. It requires some skill. In PHN lasting more than 1 year. The efficacy is independent of so that the drugs penetrate into the skin. After local anesthesia. characteristics. by continuous infusion. Cryotherapy Dry ice Effective.5% procaine Topical instillation Injection into the painful site. weeks for a total of up to 5 times. Daily to once every three days for a total effective. Iontophoresis A pad soaked with a solution of lidocaine and Pain was alleviated by 40% in 2/3 of the patients methyl predni-solone is applied to the skin. Dibucaine. Subarachnoid blocks Injection of phenol or alcohol Not adequately effective. Respiratory depression 0. it is almost ineffective.2 ml of 10% tetracaine solution Effective in 40 65% of PHN cases. the more effective it is.1 Effective in 11 out of 14 cases. topical anesthetics (Xylocaine jelly and others). Xylocaine jelly Others 530 0. triamcinolone and procaine. a piece of dry ice is pressed Effective in 77% of the patients who received it onto the site. and others JMAJ. and others Physical Therapy Nerve blocks The sympathetic.Capsaicin Local anesthetics Effective in 12 out of 14 patients who had been treated for 4 weeks. The longer PHN has lasted. who received it 3. and others Acupuncture Anesthesia by acupuncture or with needles left Anesthesia by acupuncture seems to be more inserted. It is applied twice a day. The younger the patient and the earlier the treatment. and somatic ganglions are blocked with local anesthetics 10 30 times. nerve blocks are administered by continuous infusion. Nerve blocks are administered in combination with other therapies such as epidural blocks and acupuncture in some cases. No. Epidural blocks Local anesthetic agents are used alone or in It showed little effect in some studies. It is effective even if other The electric current is applied for about 30 minutes. Treatment caused a burning sensation. stellate. Blood pressure was decreased in 2. the less effective it is. The procedure is complicated. Skill is required. the duration of PHN. nerve blocks are administered at frequencies from daily to twice a week.8 times on average. It causes frost-bite . A course consists of improvement in more than 80% of patients treated 10 blocks given twice a week or it is administered in other studies.

11 A. What Is PHN? Postherpetic neuralgia is defined by the International Association for the Study of Pai n as chronic pain following resolution of ac ute 531 herpes zoster that is accompanied with skin degeneration in the affected dermatome. necessitating vario us clinical elaborations for its treatment (Table 1). it is difficult to form a clear distinction bet ween PHP and PHN. An implanted electrode is useful as a home therapy for long-standing neuralgia. surgery (interruption of the posterior root or sympathetic trunk. 1 2 times weekly to a total of 6-12 treatments). Effective immediately after irradiation in 39 out of 64 patients. Others Moxibustion (pain disappeared when it was repeated 8 times). PHN c ases . skin excision (effective in some studies. In recent years. However. and others are also used. No. no deci sive treatment for PHN exists.” According to this theory. Various attempts to treat PHN are outlin ed below. 24 hours later.which gives rise to vesicles and pain. Transcutaneous nerve stimulation (TENS) used to apply low frequency electric current can be performed by the patients themselves and is (low frequency therapy). in wh ich PHN is only one constituent. and therefore. November 2004—Vol. but seldom satisfactory). used to stimulate the spinal cord or the brain. However. electroconvulsive therapy (pain reduced by an electric current of 110 115 V. without side effects Laser therapy A GA-AI-As semiconductor laser is irradiated for Effective in 50 about 10 minutes once a week for a total of 10 50 times. a low reactive laser. OZAWA Thus. and others). 2000. Another view advocates that neuralgia following herpes zoster should be collecti vely considered postherpetic pain (PHP). applied for 5 seconds to the anterior temporal area under general anesthesia. and then once or twice a week 80% of patients treated 4 20 times. and effective in 12. tr ansition to PHN is presumed to occur about o ne month after the onset of herpes zoster an d to persist thereafter. radiofrequency thermocoagulation (may be effective in patients not responsive to other therapies). there is concern that the prevalenc e of herpes zoster and PHN will increase further. Bunkodo.110–114) JMAJ. in many case s of herpes zoster. Liquid nitrogen Apply liquid nitrogen with a cotton ball once or Effective in 70 twice a week or once a day for 2 weeks. pp. 47.700 nm (mainly 970 nm) is irradiated for 30 minutes (temperature at the surface of the skin: 39°C). neuralgia as a form of PHP may be present for 2–3 months after the successful treatment of eruptions. This view rega rds PHN as “deafferentation pain due to n erve 3) degeneration. and others 90% (Source: Reference 5: Dermatology Practice 10. Under these circumstances. effective antiviral ag ents developed for the treatment of herpes zos ter have been used in outpatient clinics with fav or2) able clinical results. Transepidermal nerve stimulation An active electrode attached directly to the skin is Effective in 78%. An Nd-YAG laser. Near infrared irradiation Infrared light at a wavelength of 700 1.

present an issue in evaluating the cli nical efficacy of a particular treatment. 1. laser therapy. iontophoresis. Current status and expected efficacy o According to the report. Therapies from which high 532 JMAJ. 47. (1) Instructions for daily life i) Patients should not be made anxious or given preconceived ideas about pain and PHN at the onset of herpes zoster. Treatment policies for PHN The basis of treatment for PHN cons ists of medical intervention and detailed instr uctions given to individual patients and t heir 5) families. No. and ner PHN ve block therapy. eutic efficacy of various anti-pain procedures for Treatment of PHN PHN were investigated and a report issued. psychotropics. no clear treatment has been est ablished for PHN. although various procedu res have been elaborated and employed. therapies noted f or f their therapeutic efficacy and frequent clini anti-pain procedures cal Surveys of anti-pain procedures used for use include NSAIDs. patients be examined at least 3 mon eys. psychother apy. However. and rehabilitation training. ths the current status and expected therap 4) after the onset of herpes zoster. Medical treatment alone often may be insufficient. ii) Patients should be instructed to re turn to normal daily activities after erupti ons . ster oids. 2. 11 efficacy was expected despite limited ac tual use included narcotic analgesics. On the basis of these surv PHN. November 2004—Vol. Consultati on were carried out in Japan in 129 accred among anesthesiologists and dermatologists ited in facilities of anesthesiology and 259 accredi Japan has resulted in the recommendation th ted at. facilities of dermatology by the respective a when examining the efficacy of treatment ca4) for demic societies.

if there is no serious impediment to daily li ving. symptomatic treatment with NSAI Ds and vitamin B preparations should c onstitute the core treatment. aggressive anti-pain pr ocedures including physical therapies such as nerve block should be employed. while exercising caution with regard to the possible adverse effect s of prolonged use.sts.family members. ii) Up to 6 months after the cure of erupti ons Drug treatment using NSAIDs. (4) Treatment of elderly patients Elderly patients account for a considera ble proportion of all patients with PHN. the degree of its severity gradually decreases. i) Up to 3 months after the cure of eruptio ns Although neuralgia as a form of P HP remains in many patients. personality. Antiviral agents are unlikely to have therap eutic efficacy for PHN. iii) More than 6 months after the cure of er uptions Combined therapy including drug tre atment and physical therapy should be employed. acupuncture. i) Since no decisive treatment currently exi iii) Instructions in the creation of a pain. or antidepressant drugs. The goal of treatment should be to restore the patient’s ability to carry out d aily activities such as eating. i) Is it truly PHN? It is possible that any pain in patients who . (3) Choice of medical treatment Treatment should be chosen for each patie nt according to his or her symptoms and ph ase of illness. circu ii) A combination of several treatments may mbe necessary in some cases depending stances. Therefore . vitamin B preparations. When ther e is severe pain. Particul ar attention to the following points is importan t in the treatment of this population. In principle. sleeping. iii) The treatment chosen should be evaluat ed frequently to avoid its continued use mer ely because the patient complains of pain. the status of pain should be assessed obj free environment should be given to patien ectively and treatment chosen according ts and their families. there are no symptoms. laser therapy. and physical therapy including nerve b lock therapy. and so on. and iontophoresis therapy should be tried as monotherapy or combined therapy. and relationships wi on th have been cured. based on the patient’s lifestyle. Suggestions should to be the individual patient. (2) Medical treatment restrictions on daily life activities.

preoccupied with pain and the fear of pain. It therefore is necessary for patients and their families to better und erstand the patient’s response to pain and to reconsider the living environment. iii) Assessment of pain The assessment of pain in elderly patie nts can be difficult. iv) Dependence on treatment Elderly patients characteristically exhi bit intense anxiety in regard to the cessation or alteration of treatment. often leading to difficulti es in understanding symptoms. The physician in charge should always try to assess the patient’s pain objectively and make cert ain that the patient understands the need to continue. . ost eo- TREATMENT OF P O S T HE R P E T I C NEURALGIA (PHN ) arthritis. ii) Psychological dependence Patients with PHN tend to be isolated fro m social life. or terminate treatmen t. Fracture pain. The physici an should strive for objective assessment of the patient’s pain. secondary muscle ache deri ved from pain-limited motion. and pain fr om other diseases such as cardiac disease may be reported as PHN by the patient.have had herpes zoster may be wro ngly attributed to PHN. taking into account his/ her speech and actions in the consultation ro om or reports from family members regardi ng the patient’s daily life. change. and psychologically depende nt on others.

1. the skin.0 mA. refer to BS Medical.8 tion is introduced into the body painlessly v ses5) ia sions of therapy. 30.110–114. +81-3-3299-6425. 2000. Return electrode (1% sodium nitrate) 1. 11 533 clinical results. Tel. hypertension.) pain persisting for more than one year. Over two-thirds of more th an A. 47. Bunkodo.000 patients with PHN (mean duration Iontophoresis therapy is a method of topic of al PHN. 1). he The treatment was effective in patients Department of Dermatology. No. with favora ble JMAJ.6 months) showed 40–100% drug delivery by which ionized drug in a sol improveument in neuralgia after an average of 3. or diab etes mellitus. OZAWA Step 1 1. 1 Iontophoresis for postherpetic neuralgia (Source: Reference 5: Dermatology Practice 10. For Information about the instrument.(5) Iontophoresis therapy for PHN 1. 10 minutes ( ( ) ) 10 min. and its e We have carried out iontophoresis thera ffipy cacy is not affected by the duration of P using lidocaine and methylprednisolone in t HN.0 mA Step 2 Site to be treated (Mixture of lidocaine and epinephrine) 1. a nd those who had underlying diseases such as malignant tumor. Site to be treated (Methylprednisolone solution) The pad for the return electrode is used without exchange. th ose who did not respond to other treatments. Tokai Universit with y School of Medicine (Fig. 10 minutes ( ) ( ) 10 min.0 mA. Follow-up of patients for 1–5 y ears after the end of therapy confirmed a contin uing . pp. November 2004—Vol. This form of therapy is painless.0 mA Fig.

11 agents with excellent clinical efficacy have been ® developed. and Arasena A and Is Prevention of PHN Possible? TREATMENT OF P O S T HE R P E T I C NEURALGIA (PHN ) Table 2 Immunogenetic Analysis of VZV Herpes zoster PHN ® Disease resistance: HLA-B*5101 Disease resistance: HLA-B*4001 Disease resistance: HLA haplotype (A*3303-B*4403-DRB1*1302) Zovirax as intravenous preparations. there is currently no absolu important issue to be considered when a te paprophylaxis for PHN.6) 1. No. Herpes zoster should be mitigated throu gh 8) early-phase antiviral drug therapy. and th ose s a clinically useful therapeutic option. Therefore. iontophoresis therapy for PHN i Varicella vaccine is promising. M who are of an age susceptible to herpes zos ter. Antiviral 534 JMAJ. . Clinical trials of this procedure h ave ess of iontophoresis therapy for the treatment been carried out in the US as well as Ja pan. indicating the usefuln nity. Prevention of PHN in herpes zoster Prevention of the occurrence of PHN is an Unfortunately. 50–55 years of age.e. including Arasena A ointment as ® topical therapy. any other therapies have been reported to be l i. PHN. One re port has documented a 50% decrease in the incidence of PHN after antiviral drug treat ment for herpes zoster. since P tient has already contracted herpes zoster. Zovirax and Barutorex ® as ® oral preparations. 2. of with benefits reported. November 2004—Vol. The main point of treatment is to use these antiv iral agents in the early stage after onset. HN (1) Antiviral drug therapy in the early ph occurs as a sequela to herpes zoster. However. the ase of preherpes zoster vention of herpes zoster is useful.. should be inocul ated ess effective in patients with neuralgia persist with varicella vaccine to obtain booster im muing 7) for at least one year. 47. Prevention of herpes zoster therapeutic effect.

renal function is an important issue. Dosage regim ticularly those with limb lesions. sus(2) Proper topical therapy for skin lesions ceptibility and genes controlling resista Dermatologists should select an appropria nce te (Table 2). D tions have subsided. ding (3) Aggressive treatment of neuralgia vaccination. In this regard. Rehabilitation train ing ose adjustment is necessary for elderly patients should also be considered in some cases. ens of intravenous formulations are described Prediction of Onset of Herpes Zoster in and PHN detail in the manufacturer’s instructions for If PHN derives from nerve degenerat use of the drug. In addition.. recreation. the body’s immune response (sensi renal function is present. and nutrition are necess practice. Therefore. instructio en ns for daily life that emphasize the importance developed and are in widespread use in clini cal of rest. to . nine and if such differences were clarified. Results confirmed not covered by health insurance in some ar the eas involvement of HLA antigens in disease of Japan (e. Neuralgia should be treated as needed. If there were immunogenetic differences In actual practice. inclu 2) provide instructions as to its use. may and become possible by various means. prevention of their onset ence to the particular disease stage. Kanagawa Prefecture). we examined the HLA a It should be noted that the combined use ntiof gen gene region on the short arm of chro topical and oral antiviral drugs or topical a mond some 6 for genetic control of the im intravenous drip administration generally mune 9) is response to VZV. When impaire virus d ( VZ V ) . Howe ver. serum creatinine cleara in nce patients affected by varicella. (4) Instructions for daily life Antiviral agents for herpes zoster have be For patients with herpes zoster. the dose is d tiveterity) to VZV may be involved in disease on mined according to serum creatinine clearan set. although the efficacy of these antiv iral ary. and the treatment of pati ion ents resulting from invasion of varicella-zoster should follow these instructions.g. in Conclusion cooperation with an anesthesiologist. patients should be instructed agents for PHN has been denied. zoster. and P can be estimated from the serum creati HN. with ref be erpredicted. paror those who have renal disease. 2) according to a simple formula.In dosage regimens of antiviral drug thera return to their usual everyday life after e ruppy. if these diseases can topical preparation for eruptions. ce. the o level and the patient’s body weight and nset age of disease might be predicted.

178. 28: 38–40.: What is postherpetic neuralgi varicella vaccine to boost varicellaa? specific Q & A in Diagnosis and Treatment of Herpe immune responses in seropositive people s 55 (ed. Y. (in Japanese) 09– 4) Miyazaki.) Bunkodo.: Postherpetic neu ralREFERENCES gia.: Appropriate do Japanese) s6) Ozawa. 47. OZAWA 5) Sasao.: Diagnosis and to-Treat Skin Diseases (ed. M. et al. M. Tokyo. 4 and pp. 11 535 A. taki ng JMAJ.: Report of a questionnaire surv S 112. J Infect Dis 1998. J Dermatol 1999.: Follow-up of clinical age regimen of antiviral drug therapy a efficacy nd of iontophoresis therapy for postherp instructions for active daily living after cure oetic f neuralgia (PHN). et y al.methods of dealing with patients and the usa into account both the prediction and prev ge enand place of antiviral agents in the actual cli tion of the onset of herpes zoster and PHN. Rinsho To Yakubutsu Chiryo 2001 10. Tokyo. and Ozawa. Miyazaki 1753. Book Derma 1999. pp. (in Japanese) (in 2) Mabuchi. pain. 199 ster 3. T. .J. 2000. Tokyo. A. November 2004—Vol. and Ozawa. et al. Monthl . and Ozawa. T. . No. T.: Treatment of herpes z on the concept of herpes zoster-related oster. Hashimoto. (in Japanese) susceptibility to postherpetic neuralgia (PHN ). (in Japanese) T. K treatment of postherpetic neuralgia. A. 196–197.: HLA A 33 and B 4 . effect. et al. A. 110–114. . Nippon Ishikai Zasshi 1997. et al.: Use of a live atten 20: 1046–1050. Dermatology Practice 10: Diffi cult1) Iizuka. 117: 1749– Pain Control of Herpes Zoster (ed.) Research Institute of Cliniyears of age and older: duration of boo cal Therapeutics and Medicine.) Torre Lazur McCann. A. 26: 1– eruptions. 5–10. A. ey 8) Ozawa. (in Japanese) uated 3) Miyazaki. 7) Levin. Niimura. M. 1999 9) Ozawa. Suppl 1: S 1 pp. Tissue Antigens 1999. nical setting should be considered further. A. 53: 263–268.

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47. November 2004—Vol. No.536 JMAJ. 11 .