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11 Articles in Volume 10, Issue #9
Activated Glia: Targets for the Treatment of Neuropathic Pain
Acute Herpes Zoster Neuritis and Postherpetic Neuralgia
Acute Treatment of Cluster Headache
Chronic Overuse Sports Injuries in the Adolescent/Pediatric Population
Clinical Recognition of Central Abnormal Neuroplasticity
H-Wave® Stimulation: A Novel Approach In Electromedicine
Homeopathy Enters Contemporary Pain Practice
Immune-modulating Effects of Therapeutic Laser
Pain and Addiction: Words, Meanings, and Actions in the Age of the DSM-5
Partial Plantar Fasciectomy With Autologous Platelet Concentrate
Tethered Spinal Cord Syndrome: Pathophysiology and Radiologic Diagnosis

Acute Herpes Zoster Neuritis and Postherpetic Neuralgia

Dr. John Nelson is both a highly respected pain physician as well as a personal friend. We are fortunate to have him write this article on an important and often over-looked treatment for a common pain problem. Shingles/PHN is said to be the second most painful condition known to man (trigeminal neuralgia being the first) and few physicians are aware that there are simple interventions to both treat the pain and prevent occurrence of PHN. Presented here are some of those interventions.

Acute herpes zoster neuritis and postherpetic neuralgia continues to be one of the most painful, acute and chronic conditions to afflict mankind. It will continue to be a major health problem as the baby-boomer generation in the United States ages and is at risk for the reemergence of the varicella zoster virus. The impact of the chickenpox vaccine has yet to be known on the ultimate expression of this disease. As is well known, acute herpes zoster neuritis is the reemergence of the varicella zoster virus, or chickenpox virus, which has been dormant in the sensory dorsal root ganglia of the nervous system since childhood infection. Herpes zoster is a disease of the elderly as an expression of the loss of immune surveillance related to aging. With the decline in cell-mediated immunity, the virus awakens in the dorsal root ganglion and causes an intense inflammatory response with a ganglionitis. The virus eventually reaches the sensory root and travels through the nerve, eventually reaching the skin in one or, occasionally, two dermatomes and with the development of the typical blistering rash and vesicles so that the diagnosis is self-evident.

The disease is certainly more common in patients with immune deficiency such as AIDS, lymphoma, leukemias, high dose corticosteroids, or immunosuppression from cancer therapy. Usually once the virus has reawakened, the immune response contains it to one or two dermatomes and, if there is widespread dissemination, it suggests a significant defect in immune function. Many clinicians feel that the presence of herpes zoster in the younger population warrants an investigation for an occult malignancy or other problems with cell-mediated immunity.


Acute herpes zoster is the most common neurological disorder in the United States, is equally prevalent in both sexes, and probably is more severe in diabetics. The incidence of acute herpes zoster is 125 cases per 100,000 and is more common as the person gets older. The percentage of patients who will have recurrent herpes zoster—with half at the site of their original eruption—is less than 5% to 8% implying that once the immune system responds to the re-exposure to the virus, it is sufficient to last the life of the patient. Less than 11% of patients may have the syndrome with pain but without the rash. The onset of pain may precede the rash by as much as one to two weeks and may pose diagnostic dilemmas in patients. The most common area of involvement is the thoracic region followed by the ophthalmic division and clearly many patients have been evaluated for pleurisy, cholecystitis, acute myocardial infarction, etc. before the diagnosis was self-evident with the appearance of the rash. Rarely, the ganglionitis can involve other parts of the central nervous system including motor fibers such as the Ramsay Hunt’s syndrome with facial weakness due to involvement of the 7th nerve and the geniculate ganglion and there have been rare reports of myelopathy. Other complications include dermatologic dissemination, varicella encephalitis, pneumonitis, blindness due to corneal scarring from ophthalmic zoster and localized or systemic infection at the breakdown of the skin barrier.

Persistent Pain

The most common complication is postherpetic neuralgia, which is persistent neuropathic pain after the eruption is healed and usually occurs in about 3 to 4 weeks. Most clinicians, by definition, label postherpetic neuralgia as persistent pain at six weeks beyond the acute phase of the disease. The percentage of patients who will develop postherpetic neuralgia increases with the age of the patient and one study quoted 50% at age 50, 60% at age 60 and 70% at age 70, etc. The duration of postherpetic neuralgia may be months to years and the pain may be mild to excruciating to the point of placing patients at risk for suicide. Postherpetic neuralgia is the most common cause of suicide in patients with chronic pain over the age of 70 in the United States and Western Europe. As I mentioned, it is most common in the thoracic and ophthalmic distribution but can occur in any dermatome.


The treatments for acute herpes zoster and postherpetic neuralgia have been myriad in the literature and include corticosteroids, opioids, antiviral agents, small pox vaccination, topical local anesthetics and capsaicin and even iontophoresis vincristine. What is clear is that the acute phase of acute herpes zoster neuritis seems to have a significant sympathetically-mediated component and the development of postherpetic neuralgia represents the evolution of this condition to a sympathetically-independent neuropathic condition that can be very resistant to treatment. This resistance to successful management is certainly represented in the high incidence of suicide. There are some early studies suggesting that aggressive treatment of the acute pain with analgesics, including opioids, may decrease the percentage of patients with postherpetic neuralgia. With the development of antiviral medications—such as acyclovir, famiciclovir, etc.—it was hoped that there would be a significant impact on the percentage of patients with postherpetic neuralgia but this has not been shown to be the case.

The drugs, if given during the acute phase, probably decrease the amount of viral shedding and the development of new lesions and the duration of postherpetic neuralgia but do not decrease the frequency or incidence of postherpetic neuralgia. This will be discussed in the next several paragraphs and probably represents the fact that the inflammatory response to the varicella zoster virus is the major factor in the development of post-herpetic neuralgia. This response probably occurs even to viral particles in sera—even when the virus has been killed.


As anesthesiologists, we have long recognized and felt passionately about the role of neural blockade and especially sympathetic blockade in the treatment of acute herpes zoster neuritis. This was first written about in 1938 by Dr. Rosenak, a practicing physician in Budapest, Hungary. Dr. Rosenak was a dermatologists whose next door neighbor was an orthopedic spine surgeon who was seeing a patient for peripheral vascular disease and had performed a diagnostic lumbar sympathetic block to determine if the patient’s pain was amenable to sympathectomy. The patient, coincidentally, had acute herpes zoster lesions on the buttock and, following the sympathetic block, reported to the surgeon that the lesions had crusted over, dried up and his pain was essentially gone. When this was reported to Dr. Rosenak, he subsequently compiled a series of 21 patients with acute herpes zoster whom he treated with sympathetic blockade with local anesthetic. Of these, 19 patients had immediate and permanent relief of their pain with one block and one patient with two blocks. This represented a 95% success rate. Dr. Rosenak published his work in Lancet in 1938.1

Subsequent investigations into this modality of treatment were by Dr. August Colding in Sweden who probably published the largest series.2 Dr. Colding’s work clearly suggested that the best response to sympathetic blockades were in patients with early herpes zoster. Over the next 20 years, similar pain specialists have recognized the validity of this including Dr. Bonica who stated in his text book of chronic pain that early sympathetic blockade should be part of the standard of care of acute herpes zoster.3 This certainly fits with our recommendations that almost all acute sympathetically mediated pain syndromes do best with early interruption of the sympathetic afferent and efferent.

One of the best studies is by Dr. Alon P. Winnie from Chicago who had a series of 122 patients seen at varying intervals after the onset of their acute herpes zoster neuritis and included a two year follow-up. As Dr. Winnie’s data shows, the dramatic relief with one or a short series of blocks again occurred in patients who were seen early in the course of their disease with there seeming to be drop-off of response at about eight weeks (see Figure 1). There are now over 50 articles in the literature attesting to the efficacy of early sympathetic blockade in acute herpes-zoster—not only providing immediate palliation of the pain as well as shortening of the progression of the lesions but also supporting a significant decrease in postherpetic neuralgia. Dr. Winnie’s data suggest the decrease was up to 80% in a population of elderly patients who were at risk. There is one double blind control study from the Clinical Journal of Pain by Dr. Tenicele reporting on a series of 20 patients.4 One group of 10 was given sympathetic blocks with local anesthetic and the other group was given placebo. After four blocks, the code was broken and those who still had pain were given local anesthetic blocks and the overall success rate was 90% relief of the acute pain and prevention of postherpetic neuralgia. Although the study was small, it did reach statistical significance.

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The question that is often asked is: Why should sympathetic blockade early in the course of a viral ganglionitis and neuritis be effective in preventing postherpetic neuralgia? We know from histological data at autopsy, on patients with terminal cancer who had acute herpes zoster, that the initial ganglionitis and neuritis involves a marked inflammatory response—sometimes with even hemorrhagic necrosis. Early on, there is interstitial edema that results in increased intraneural pressure and vasoconstriction of the vaso nevorum5 and sympathetic efferent stimulation. This neural ischemia, if prolonged, has been shown to result in irreversible damage of the nerves which probably explains why, if not relieved promptly, results in a postherpetic neuralgia that then becomes relatively resistant to sympathetic blockade.

Dr. Selander has written about the presence of neural ischemia and reduction of intraneural capillary blood flow by up to 95%. This work has also been supported by the work of Dr. Lundborg who is a Swedish hand surgeon who was looking at the effect of prolonged ischemia on peripheral nerves.6 He was ligating the nerves for variable periods of time resulting in nerve ischemia. This data seemed to show that at about eight weeks, the ischemic changes started to become non-reversible—especially in large fibers. Dr. Fink has corroborated some of this data by showing that hypoglycemia and hypoxia seems to preferentially result in the demise of the larger myelinated fibers probably by virtue of their greater metabolic rate.7 This work was then written about by Nordenbos who was a neurosurgeon in Holland who biopsied the intercostal nerves of a group of five patients with postherpetic neuralgia.8 He also talked them into letting him biopsy the normal intercostal nerve, which today would certainly raise concerns about creating a causalgia.

What Dr. Nordenbos described was the concept of fiber disassociation where there seemed to be a predominance of small non-myelinated C-fibers in the postherpetic neuralgia patients and a loss of the larger myelinated fibers. Wall and Malzack’s Gate Theory of Pain was, in part, based upon the work of Dr. Nordenbos and, when they published their paper six years later, their theory clearly stated that the tonic influence of neural activity of large myelinated fibers seem to suppress pain through the smaller non-myelinated C-fibers. The loss of these fibers may explain the neuralgia seen in postherpetic neuralgia and may account for why peripheral nerve stimulation with a TENS unit has been shown to be fairly ineffective in this condition. The fact that the pain is also spontaneous and may be burning with hyperpathia, allodynia, etc., is explained by the lack of the inhibitory effect of large fibers in the peripheral nerve.


It seems that the use of sympathetic blockade early on may prevent the irreversible neural ischemia and terminate the acute pain of herpes zoster by preventing irreversible nerve damage and, hopefully, prevent permanent postherpetic neuralgia. Dr. Winnie’s data clearly show that, even in the patient who is months out with their postherpetic neuralgia, it is worthwhile trying a sympathetic blockade because occasionally you will have a responder, and for that one patient, the success rate is 100%. The problem of chronic postherpetic neuralgia is the fact that once the nerve has been irreversibly damaged, the treatment success rate with any number of therapies is poor and difficult to predict. Furthermore, some of the therapies, especially in the elderly population, may be poorly tolerated due to side effects.

Palliative Care

In addition to trying sympathetic or sensory neural blockade, including epidurals, much has been written about low dose tricyclics or phenothiazines and the use of membrane-stabilizing anticonvulsants, again, with variable success from one patient to the next. Postherpetic neuralgia as a sympathetically independent neuropathic pain has been reported to be relatively opioid resistant. There are patients treated with low doses of opioid such as methadone who have had some relief of their pain, especially when these were used in conjunction with anticonvulsants and tricyclics. Variable success has been reported with topical capsaicin, topical aspirin mixed with chloroform, other solvents, topical local anesthetics, TENS stimulation, and even some reports in the Italian literature of iontophoresis with vincristine (a neural toxic) as a chemotherapeutic agent. Neurolytic or neuroablative techniques such as neuroectomy, peripheral injections of alcohol, phenol or cryo-neurolysis of the peripheral nerves have been uniformly disappointing and, probably, even increased the risk of unnecessary deafferent pain. Dr. Racz has had some experience with repeat epidural phenol injections with some patients with fairly long-term relief but this usually involves more than one series of injections. Dorsal root entry zone (DREZ) lesions have also used in the treatment of this condition. Again, there is significant risk involved in some of these procedures.

The use of intraspinal agents such as opioids and local anesthetics have had some success, especially when adding local anesthetics to the level of segmental block. Now that we have intraspinal Catapres« (clonidine) and investigational studies with SNX 111, it will be interesting to see if these agents have any role in the treatment of chronic postherpetic neuralgia and whether clonidine has a role in any future studies as part of the treatment of acute herpes zoster with the addition of epidural clonidine to our blocks. Since it is not approved for use above the T4 dermatome, it cannot be used in cervical or head and neck acute zoster.

The use of dorsal column stimulation and, more specifically, entry zone stimulation has had some success in the treatment of this condition and clearly is worth trying since it is reversible and neuroaugmentive. Dr. Racz has shown that dorsal column stimulation alone is usually not effective and that one needs to actually stimulate near the dorsal root entry zone at the segmental level of the involved peripheral nerve.


It appears that the optimum treatment for chronic postherpetic neuralgia, which has been described as a belt of roses from hell, is to effectively treat the acute herpes zoster neuritis. This involves the prompt use of antivirals, analgesics and sedatives to help with sleep and acute pain, together with early and aggressive sympathetic block, to try to prevent and reverse neural ischemia and permanent nerve damage. Obviously, the use of these techniques involves education on our part of our colleagues in primary care, dermatology, ophthalmology and oncology, and letting them know of the considerable literature showing the appropriateness and efficacy of these modalities of treatment in those patients with herpes zoster who are certainly at risk for developing chronic and intractable pain.

It is equally incumbent upon us to be available, on short notice, to attend to these patients. The earlier we can intervene, the better chance we have of making a significant impact on this incredibly painful condition that often leads to many of these patients choosing suicide over having to continue to live with the unrelieved pain and suffering of this condition.

Last updated on: April 11, 2012
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