Herpes Zoster Pain Research Articles

Tolerability of Treatments for Postherpetic Neuralgia

Herpes zoster occurs in up to 20% of people infected with varicella-zoster virus, due to reactivation of the virus from latently infected sensory ganglia. Although pain is a typical feature of acute zoster, pain persisting for more than a month after resolution of the rash is less common and is termed postherpetic neuralgia (PHN). The pain associated with PHN is neuropathic in origin and is notoriously difficult to treat. The incidence of herpes zoster and its associated complications both increase with age, so PHN should be seen more commonly in an aging population. Vaccination with live, attenuated varicella vaccine is safe and efficacious, particularly in children. It decreases the incidence of acute varicella and subsequent herpes zoster. Aciclovir is well tolerated, with renal toxicity only at high intravenous doses. Treatment of acute varicella with aciclovir attenuates acute illness but does not prevent herpes zoster. Treatment of herpes zoster with aciclovir or its derivatives minimises symptoms and may reduce the rate of PHN. Foscarnet is an alternative for an aciclovir-resistant virus but its use is limited by renal and CNS toxicity. Corticosteroids reduce acute pain in herpes zoster but do not affect the incidence of PHN. Their use in some patients may be limited by adverse effects such as gastritis and impaired glucose tolerance. Treatment of established PHN is difficult and may require a holistic approach. Tricyclic antidepressants and gabapentin are the systemic agents with the most proven benefit, although opioids such as oxycodone and NMDA receptor antagonists such as ketamine may be useful in some people. Adverse effects from tricyclic antidepressants are common but usually mild, while gabapentin is generally well tolerated. Although effective, the relatively common adverse effects of opioids and ketamine limit their usefulness in treating PHN. Topical treatment with 5% lidocaine patch or capsaicin is of benefit in some patients and is generally well tolerated. Intrathecal methyl prednisolone may be considered for intractable pain but efficacy and safety have not been confirmed.

Paralysis due to Spinal Cord Tumor Found during the Management of Postherpetic Neuralgia

Herpes zoster results from a reactivation of latent varicella-zoster virus in the dorsal root ganglia, and is frequently associated with severe pain. The pain of herpes zoster gradually resolves with time, but may persist after the acute disease as postherpetic neuralgia for weeks, months, or even years. Postherpetic neuralgia is difficult to manage and, unfortunately, is refractory to most treatment modalities. A 68-year old female patient with polyneuropathy as a result of diabetic complications, had been controlled for blood sugar level with an oral hypoglycemic agent for 5 years. She had also has suffered from postherpetic neuralgia on 7th thoracic dermatome of her right flank area for 4 months. We report a spinal cord tumor revealed during an evaluation of lower extremity weakness after thoracic epidural block for the management of postherpetic neuralgia.

The Efficacy of Continuous Epidural Blockade with Ketamine and Local Anesthetics on Acute Herpes Zoster Pain: A case report

The pain associated with acute herpes zoster is neuropathic. In this case report, we describe acute herpes zoster patients with severe pain, allodynia, and hyperesthesia over the to TEX>$T_8$ dermatomes. Patients received continuous epidural administration of ketamine at a dose of 20 mg with 0.125% bupivacaine at a dose of 110 ml for 2 days. Their acute herpes zoster pain was controlled without any sign of side effects. This case report, epidural blocks with ketamine, an antagonist of the N-methyl-D-aspartic acid receptor and bupivacaine effectively in treated acute herpes zoster pain, when applied soon after the onset of the acute phase of the disease.

The Role of Antivirals in the Management of Neuropathic Pain in the Older Patient with Herpes Zoster

Herpes zoster has been known since ancient times. It is a ubiquitous disease, occurring sporadically without any seasonal preference and is caused by the varicella-zoster virus. It may be defined as an endogenous relapse of the primary infection varicella. Herpes zoster is characterised by typical efflorescences in the innervation region of a cranial or spinal nerve and starts and ends with pain of varying intensity. Currently, several antiviral drugs are approved and many studies have shown that antiviral therapy, started early in the course of disease, can significantly reduce the risk and the duration of postherpetic neuralgia in elderly patients. The effects of all antivirals discussed in this article, given either orally or intravenously, are comparable with regards to the resolution of virus replication, prevention of dissemination of skin lesions and reduction of acute herpes zoster pain. Valaciclovir (valacyclovir), famciclovir and brivudine (brivudin) are comparably effective in the reduction of the incidence and/or prevention of zoster-associated pain and postherpetic neuralgia. Brivudine 125mg once daily is as effective as famciclovir 250mg three times daily in reducing the prevalence and the duration of zoster-associated pain and postherpetic neuralgia, especially if therapy is combined with a structured-pain therapy. The intensity of the therapy for pain should depend on the intensity of the pain that it is treating. Famciclovir and brivudine offer an advantage over other antivirals because they are administered less frequently; this is particularly relevant for elderly patients who may already be taking a number of medications for other diseases. Therefore, antiviral therapy in combination with adequate pain management should be given to all elderly patients as soon as herpes zoster is diagnosed.

Consequences and management of pain in herpes zoster.

Postherpetic neuralgia (PHN) is a common complication of herpes zoster, particularly in the elderly and in persons with severe symptoms at presentation. Unless varicella vaccination reduces the incidence of herpes zoster and attenuates the risk and/or severity of complications, PHN will continue to result in significant suffering and remain a consumer of health care and related social support resources. Although there have been useful advances in the management of PHN (e.g., the use of the anticonvulsant gabapentin), some cases remain intractable. Prevention remains the preferred strategy, and antiviral drugs are the most well established means of preventing the development of pain. Other interventions require further evaluation (nerve blocks, acute-phase tricyclic antidepressant or anticonvulsant use). Because prevention of PHN requires early recognition and prompt management of patients presenting with herpes zoster, public education and dissemination of information to all health care personnel involved with the disease are essential.

Understanding pain in herpes zoster: an essential for optimizing treatment.

After herpes zoster, immunocompetent persons frequently experience chronic pain and considerable suffering. Zoster-associated pain has a complex pathophysiology that begins with viral damage and increased sensitization of peripheral sensory neurons. The enhanced afferent barrage from these neurons sensitizes spinal neurons and leads to loss of synapses from descending inhibitory fibers, resulting in central neuropathic pain and allodynia. Antiviral therapy of acute zoster limits this sequence of pathophysiologic mechanisms. There is no clear consensus regarding the optimal means of determining the benefits of antiviral therapy in the management of pain of herpes zoster. A novel statistical approach utilizing rates of disappearance of pain of differing pathophysiologic mechanisms is proposed.

Spinal cord stimulation in postherpetic neuralgia and in acute herpes zoster pain.

We studied the effects of spinal cord stimulation (SCS) on postherpetic neuralgia (PHN). Data of 28 patients were prospectively investigated over a median period of 29 (quartiles 9--39) mo. In addition, four patients with acute herpes zoster (HZ) pain were studied simultaneously. After intractable pain for more than 2 yr, long-term pain relief was achieved in 23 (82%) PHN patients (median, 70 yr) during SCS treatment confirmed by a median decrease from 9 to 1 on the visual analog scale (P < 0.001). In five cases with serious comorbidity, the initial pain alleviation could not be stabilized. Spontaneous improvement was always confirmed or excluded by SCS inactivation tests at quarterly intervals. Eight patients discontinued SCS permanently because of complete pain relief after stimulation periods of 3--66 mo, whereas 2 reestablished SCS because of recrudescence after 2 and 6 mo. Considerable impairments in everyday life, objectified by the pain disability index, were also significantly improved (P < 0.001). In 4 patients with acute HZ pain, SCS was promptly effective and after periods of 2.5 (quartiles 2--3) months the pain had subsided. SCS seems to offer a therapeutic option for pharmacological nonresponders. In many patients with postherpetic neuralgia and acute herpes zoster pain is not satisfactorily alleviated with pharmacological approaches. We report on 23 of 28 patients with postherpetic neuralgia and 4 of 4 with acute herpes zoster whose chronic pain was improved by electrical spinal cord stimulation.

Clinical correlates of prolonged pain in Japanese patients with acute herpes zoster.

To determine which risk factors are relevant to the occurrence of post-herpetic neuralgia in Japanese patients with acute herpes zoster, correlations between the prolongation of pain and various disease factors were examined in 263 adult patients presenting within 10 days of the onset of rash at 17 institutions in the Hyogo region of Japan. All patients in whom pain persisted for more than 3 months were over 60 years of age. The pain also tended to be more prolonged in those with clustered vesicles, disturbed sleep and hypanaesthesia. Other factors such as underlying disease states, critically involved regions, scar tissue, generalized rash and allodynia were not relevant to the duration of pain. Although decreased pain persistence was observed in patients in whom acyclovir therapy was initiated within 72 h of the onset of symptoms in comparison with those in whom it was initiated after this time, the difference between the two groups of patients was not statistically significant. Our results suggest that advanced age, the presence of clustered vesicles, and disturbed sleep and hypanaesthesia influence the prolongation of herpes zoster pain.

Is an Epidural Steroid Injection with an Addition of an Intravenous and Intradermal Injection of Lidocaine Advantageous in the Pain Management of Herpes Zoster?

Background: An epidural blockade has been considered a standard therapy for the management of pain in acute herpes zoster. However, it has many complications. Recently, we experienced good analgesia with a combination therapy including intravenous lidocaine infusion and intradermal injection of a local anesthetic and steroid in acute herpes zoster. Therefore, this study was performed to evaluate the necessity of an epidural steroid injection, added in a combination therapy, on the pain control of acute herpes zoster. Methods: This retrospective study was based on the analysis of data of medical records. Forty-three patients suffering severe acute herpes zoster pain, were randomly divided into two groups. Intravenous lidocaine infusion (5 mg/kg) and an intradermal injection of lidocaine and a steroid into the wound were used twice a week in the Lidocaine group (n = 23), and in the Epidural group (n = 20), an epidural block with 0.5% lidocaine 6-8 ml with triamcinolone 30 mg was added once a week in addition to the above. We compared the efficacy of pain control using a pain relief scale (PRS) at 4 weeks after the initial visit to the pain clinic. Results: Both groups were similarly managed in pain control. There were no statistical differences comparing the PRS between the two groups. Conclusions: Our results suggest that an epidural steroid injection, added in a combination therapy such as an intravenous lidocaine infusion and an intradermal injection of a local anesthetic and steroid, has no more advantages for the management of pain in acute herpes zoster. A further prospective study is recommended to compare the efficacy of pain control and the incidence of postherpetic neuralgia in a large number of acute herpes zoster patients.

Corticosteroids for herpes zoster: what do they accomplish?

For some patients, herpes zoster infections not only result in acute pain but serious consequences, including postherpetic neuralgia and damage to ocular tissues. Some authors have recommended corticosteroids for the treatment of these acute symptoms and complications. The literature concerning the use of corticosteroids for herpes zoster, however, either provides conflicting results or includes recommendations based on clinical experience rather than clinical trials. The author performed a search of the literature to address the question of whether corticosteroids are well tolerated and effective for the treatment/prevention of the acute pain of herpes zoster, postherpetic neuralgia, and/or the ocular complications resulting from herpes zoster. While smaller trials found oral corticosteroids beneficial for preventing postherpetic neuralgia, larger, better designed trials have not found oral corticosteroids to be more efficacious than placebo in preventing postherpetic neuralgia. Trials investigating the effect of oral corticosteroids for the acute pain of herpes zoster have found that corticosteroids provide a statistically significant improvement. Whether these improvements are clinically significant is uncertain. Thus, oral corticosteroids may confer a slight benefit for initial symptoms as long as the patient is not at risk for complications resulting from corticosteroid therapy. Most trials of topical and injectable corticosteroids are limited by several shortcomings. Therefore, topical and most forms of parenteral corticosteroids have yet to be proven effective for the treatment of acute pain or prevention of complications. Two controlled, blinded trials investigating the use of intrathecal corticosteroid administration for intractable postherpetic neuralgia suggest that corticosteroid administration results in a significant improvement in pain. Despite this, several authors have voiced concern over possible serious adverse events with the intrathecal administration of corticosteroids. Intrathecal corticosteroids may provide a benefit for intractable postherpetic neuralgia, but because of risks of serious complications, this is a last-line option and should only be administered by experienced personnel.

Herpes zoster--predicting and minimizing the impact of post-herpetic neuralgia.

Herpes zoster results from reactivation of latent varicella-zoster virus in the dorsal root ganglia and is frequently associated with severe pain. Most patients suffer acute pain during the rash phase, and in many, prodromal pain or discomfort also precedes the rash. The pain of herpes zoster gradually resolves with time, but may persist after the acute disease as post-herpetic neuralgia for weeks, months or even years. Post-herpetic neuralgia, the most common complication of herpes zoster, often results in significant morbidity and healthcare resource usage. Early treatment with oral antivirals has been shown to accelerate the resolution of postherpetic neuralgia, with therapeutic effects particularly evident in the over-50 age group, where pain generally persists for longer. Progressively increasing life expectancy of the population translates to increasing numbers of cases of herpes zoster. The socio-economic gains associated with active management, including use of oral antivirals where indicated, to speed resolution of pain and post-herpetic neuralgia, readily justify additional cost.

Clinical Science (43)

Valaciclovir: a review of its use in the management of herpes zoster. (Adis International Limited, Auckland, New Zealand) Drugs 2000;59:1317–1340.This study compared the effectiveness of valaciclovir (1000 mg 3 times daily for 7 days) and aciclovir (800 mg 5 times daily for 7 days) in controlling the symptoms of acute herpes zoster. Valaciclovir was found to alleviate zoster‐associated pain and postherpetic neuralgia significantly faster than aciclovir. A 14‐day regimen of valaciclovir showed no significant advantage over the 7‐day regimen. A smaller trial in Japanese patients focusing primarily on the cutaneous (rash) signs of herpes zoster confirmed the similar efficacy of valaciclovir and aciclovir in the 7‐day regime. Valaciclovir and aciclovir demonstrated similar efficacy for the control of cutaneous lesions and ocular complications in patients with zoster ophthalmicus. Starting treatment later than 72 h after rash onset did not significantly reduce the beneficial effect of valaciclovir on the duration of zoster‐associated pain, suggesting that valaciclovir might be effective when given later than previously thought. However, valaciclovir should ideally be given as soon as possible after symptoms appear. Valaciclovir was well tolerated with nausea and headache as being the most commonly reported adverse events. The adverse events profile of the agent was similar to that seen with aciclovir or famciclovir. Conclude that the efficacy of valaciclovir for the treatment of herpes zoster has been confirmed and extended by follow‐up studies in herpes zoster ophthalmicus, in Japanese patients, and in the wider primary care setting. Valaciclovir is at least equivalent to, and better in certain parameters than, aciclovir and appears to have similar efficacy to famciclovir 500 mg 3 times daily. Comment by Susan Anderson, MD.This is a review article on the antiviral drug valaciclovir. The varicella zoster virus (VZV) is commonly treated with the antiviral drug aciclovir. However, aciclovir has a low oral bioavailability that limits its efficacy in the treatment of herpes zoster. Valaciclovir was developed in order to have a more readily absorbed oral antiviral drug. When valaciclovir was compared to aciclovir in a large study, it was noted that valaciclovir was as effective in controlling the symptoms of acute herpes zoster. It was also noted valaciclovir alleviated zoster associated pain and postherpetic neuralgia significantly faster than aciclovir. Also, there was no significant advantage of treating valaciclovir 14 days versus 7 days; therefore, a 7‐day regimen is recommended. In a smaller trial from Japan that focused primarily on the cutaneous (rash) signs of herpes zoster, there was also confirmation of similar efficacy of aciclovir and valaciclovir in a 7‐day regimen. The similarity in efficacy was not only for cutaneous lesions but also for ocular complications in patients with zoster ophthalmicus. In a large controlled trial, they compared valaciclovir and famciclovir. This showed similar efficacy in resolution of acute herpes zoster rashes shortening the duration of postherpetic neuralgia. It was purposed in the article that the therapeutic window for beneficial treatment with valaciclovir and zoster associated pain may be wider that previously though. It is still recommended that valaciclovir be ideally given as soon as possible after symptoms appear. However, starting treatment after 72 hours after rash onset did not significantly reduce the beneficial effect of the valaciclovir on duration of zoster associated pain. Valaciclovir is known to be well tolerated with nausea and headache being the most commonly reported adverse events. The adverse events profile of valaciclovir is similar to aciclovir or famciclovir. The purpose of this review was to present an overview of the pharmacodynamic/pharmacokinetic properties and therapeutic efficacy in the assessment of pain in herpes zoster in comparison with known agents of aciclovir, famciclovir, and/or placebo.It is concluded that valaciclovir is an efficacious agent in the treatment of herpes zoster and herpes zoster ophthalmicus. It's at least as efficacious as aciclovir and has similar efficacy to famciclovir. It is well tolerated with a similar side effect profile as aciclovir and famciclovir.

Prospects for the prevention of postherpetic neuralgia in herpes zoster patients.

Herpes zoster is a common and painful disease that is caused by reactivation of the varicella-zoster virus. Herpes zoster pain that persists after healing of the acute infection is termed postherpetic neuralgia (PHN), a chronic pain syndrome that is often refractory to all treatment. The prevalence of PHN is expected to increase substantially in the coming decades, because the incidence of herpes zoster and the risk of PHN will both increase as the population ages. Although the results of recent studies provide a basis for improved treatment of patients with PHN, as many as half of all PHN patients do not obtain relief of their pain. Research on the development of improved treatments is continuing, but it has not been generally recognized that an equally important goal should be the design of interventions to prevent PHN. The prevention of PHN would lead to major reductions in disability, suffering, and the use of health care resources. The results of recent studies that have identified risk factors for the development of PHN and have implicated several peripheral and central mechanisms in its pathophysiology are reviewed. These risk factors and mechanisms of PHN provide a basis for hypothesizing that combining antiviral therapy with analgesic treatment beginning as soon as possible after the onset of herpes zoster would reduce the risk of PHN beyond that achieved by antiviral therapy alone. This treatment approach would be expected to reduce the risk of PHN in herpes zoster patients by attenuating acute pain and thereby preventing the initiation of central mechanisms of chronic pain.

Valacyclovir or Famciclovir for Herpes Zoster

Both valacyclovir and famciclovir effectively decrease the duration of acute pain in herpes zoster and in post-herpetic neuralgia, usually defined as pain persisting after the skin lesions have healed. This randomized, double-blind trial, sponsored by the makers of valacyclovir and conducted in …

Epidural Blockade for Herpes Zoster Pain

Duration of acute pain in herpes zoster is slightly reduced by antiviral agents begun within 72 hours of the rash, while systemic corticosteroids have

Pain and Somatosensory Dysfunction in Acute Herpes Zoster

To determine the nature of sensory change and its association with pain and allodynia in acute herpes zoster. Prospective clinical study. One hundred thirteen immunocompetent patients with acute herpes zoster. Onset, intensity, and quality of pain and severity of rash were recorded. Quantitative somatosensory testing for tactile and thermal thresholds, qualitative pinprick testing, and testing of dynamic and static allodynia were performed within the affected dermatome, its mirror-image dermatome, and in an adjacent dermatome bilaterally. Acute pain was reported as severe in 50%, moderate in 29%, mild in 12%, and absent in 9% of patients. Preherpetic pain (median = 4 days, range = 1-60 days) was experienced by 71%. Mechanical allodynia, dynamic, static, or both, was found in 37% of patients and was noted to extend one or more dermatomes outside the rash in 12%. In the affected dermatomes, thresholds were elevated for warmth and cold, lowered for heat pain, and unchanged for touch when compared with the contralateral side. Logistic regression analyses showed that compression-evoked allodynia, brush-evoked allodynia, and the history of preherpetic pain were more frequently encountered in patients with severe pain. Sensory threshold changes were not associated with the severity of pain or rash or with the presence of allodynia. Pain, allodynia, and altered sensation are common features of acute herpes zoster. They are likely to result primarily from widespread neural inflammation within the affected afferent system. The sensory changes found in acute herpes zoster are different from those reported in published studies on postherpetic neuralgia and suggest sensitization phenomena and preservation of tactile functions rather than major neural damage. The exact mechanisms for acute herpes zoster pain, however, remain speculative.

A Mixed Model for Factors Predictive of Pain in AIDS Patients with Herpes Zoster

A unifying model of herpes zoster pain presents considerable analytical challenges due to the requirement for prospective data collection and the varying rates of pain resolution reported by individual patients. Demographic, clinical, and quality-of-life measures were collected on 166 human immunodeficiency virus (HIV)-infected patients enrolled in a randomized, controlled trial of antiviral therapy of herpes zoster comparing acyclovir with sorivudine. A “mixed model” was used to assess factors predictive of pain severity, activity impairment, and sleep interruption. The average rate of change in acute pain was −0.04 unit pain per day for the first month. Chronic pain decreased −0.12 per month for months 1–12. Acute pain severity was positively correlated with number of new skin vesicles, analgesic use, and baseline pain, and negatively related to percentage of lesion healing and crusting. Postherpetic neuralgia was correlated with baseline pain, pain at 1 month, and duration of lesions. Treatment group, gender, race, and CD4 count were not related to change in pain severity. These analyses verify the significance of baseline pain as a significant predictor of pain resolution and average pain severity as a predictor of return to normal daily activities and sleep. The severity of acute pain at presentation and at 1 month are significant predictors of chronic pain.

Acute herpes zoster and postherpetic neuralgia

Herpes zoster is a common illness in aged patients that is characterized by shingles and severe segmental pain. The nature and duration of the illness is highly variable, and it is also very difficult to relieve. This review of pain in acute herpes zoster and postherpetic neuralgia analyzes clinical observations and describes new treatments that have the potential to improve the lives of patients who suffer from these two illnesses.

Postherpetic neuralgia: the importance of preventing this intractable end-stage disorder.

An argument is presented here for postherpetic neuralgia as an intractable end-stage disorder for many patients. The exciting possibility of prevention of this disorder by early, aggressive treatment exists; however, the extent to which therapy can be effective is unknown. Early, aggressive treatment of the pain of herpes zoster is, nevertheless, urged, and the options for treatment are discussed. These options include antiviral therapy within the first 72 h, if possible, from the onset of rash or radicular pain and the use of analgesics, including opioids (if necessary), nerve blocks, and early antidepressant therapy. In addition, the extent to which vaccination of older adults will prevent postherpetic neuralgia is unknown but appears to hold promise.

Methodology of evaluation of herpes zoster pain: Two different concepts, zoster associated pain versus postherpetic neuralgia

Methodology of evaluation of herpes zoster pain: Two different concepts, zoster associated pain versus postherpetic neuralgia