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Medicine » Orthopedics, Physical Medicine and Rehabilitation » "Pain Management", book edited by Milica Prostran, ISBN 978-953-51-2414-6, Print ISBN 978-953-51-2413-9, Published: May 25, 2016 under CC BY 3.0 license. © The Author(s).

Chapter 4

Pain Management of Herpes Zoster

By Hwa Young Jung and Hyun Jeong Park
DOI: 10.5772/62873

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Pain Management of Herpes Zoster

Hwa Young Jung and Hyun Jeong Park
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Herpes zoster (HZ) is a disease triggered by the reactivation of latent varicella zoster virus (VZV) in spinal or cranial sensory ganglia, and is characterized by a painful vesicular eruption in the affected dermatome. Postherpetic neuralgia (PHN) is a chronic, neuropathic pain that can persist long beyond resolution of visible cutaneous manifestations which is often resistant to current analgesic treatments. The lifetime prevalence of herpes zoster is approximately 20–30% and about 9–34% of these patients develop PHN depending on its definition. Clinical experience has shown that PHN often develops in cases of inadequate initial pain management resulting in increased pain intensity. This review provides an overview of the treatment options for HZ and PHN, focusing on the therapeutic modalities of pain management. The primary objectives of management of HZ are to inhibit viral replication, relieve pain, and prevent associated complications, such as PHN. General treatments for acute HZ are combination of antiviral therapy with a short course of corticosteroids at the onset of the disease in conjunction with an effective control of acute pain, including nonsteroidal anti-inflammatory drugs, acetaminophen, opioids, and anticonvulsants such as gabapentin or pregabalin. Treatment of PHN is often resistant to the current pharmacologic methods. Therefore, a multimodal analgesic treatment regimen including topical lidocaine and capsaicin, systemic therapies, and the interventional treatments is necessary to alleviate pain and its effect on quality of life. As the incidence of HZ increases with age, the number of patients with HZ and PHN may increase in the future considering the gradual aging of the general population. Appropriate management of HZ can reduce the duration and intensity of pain from HZ, and prevent the development of PHN. In addition, prophylactic zoster vaccination can prevent or reduce the incidence of HZ and PHN. Further efforts are needed to minimize pain of the patients suffering from HZ and PHN as it affects the quality of life in the aspect of both physical and psychological impairments.

Keywords: Herpes zoster, post-herpetic neuralgia, pain control, treatment of herpes zoster, management of post-herpetic neuralgia

1. Introduction

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in sensory dorsal root ganglion cells, and is characterized by a painful, unilateral vesicular skin eruption in the affected dermatome. The lifetime risk of HZ is approximately 15–30% [13]. The incidence of herpes zoster is 1.5–3.0 per 1000 person-years in all ages and 7–11 per 1000 person-years in persons over 60 years of age in European and North American, according to studies [19]. Classically, the skin eruption is preceded by one to several days of stabbing, episodic or continuous pain in the affected area, although the pain may develop simultaneously or even following the skin eruption. Herpes zoster-associated pain tends to resolve over time, but approximately 10–50% of herpes zoster patients develop post-herpetic neuralgia (PHN) that can persist several years beyond resolution of visible cutaneous eruptions. The frequency of PHN has been reported to be from 10% to 50% depending on its definition [10]. PHN is typically defined as persistent pain 90 days after the acute onset of HZ [3, 11, 12]. The incidence of PHN by this definition is 10–20% [3, 12]. In approximately 15% of patients with PHN, the pain persists for up to two years [13]. Mechanism to cause PHN follows a classic paradigm of other forms of neuropathic pain. Sensitization of nociceptors occurs after inflammation of dorsal root ganglia by reactivation of varicella zoster virus, leading to hyperexcitability of sensory neurons. The spontaneous discharge and lower activation thresholds provoke exaggerated responses to stimuli, resulting in allodynia and hyperalgesia. The loss of function or death of dorsal horn neurons, contributes to a connectional state of central nervous system nociceptive pathways, after anatomic deafferentation. The central sensitization is initially temporary, but may become permanent [14, 15]. Clinical experiences have shown that immunocompromised patients and elderly individuals are at an increased risk of PHN, and early initiation of antiviral treatment may reduce the incidence of PHN [16]. This review focuses on the practical overview of the treatment options available for management of patients with acute HZ and PHN.

2. Treatment of acute herpes zoster

The management of acute HZ aims to inhibit ongoing viral replication and alleviate pain. Treatment modalities for acute HZ include antiviral agents, analgesics, corticosteroids, and neural blockade.

2.1. Antiviral agents

Acute HZ is treated with antiviral agents such as acyclovir, famciclovir, and valacyclovir [1720].

These antiviral agents are nucleoside analogues which are phosphorylated by viral thymidine kinase and cellular kinases to a triphosphate form that inhibits viral DNA polymerase, leading to a decrease of viral replication. Other types of antiviral agents such as foscarnet, vidarabine, and cidofovir are not dependent on viral phosphorylation and noncompetitively block viral DNA polymerase. In general, famciclovir and valaciclovir are accepted to have higher and more reliable levels of antiviral activity and bioavailability, although there is no systematic data proving superior efficacy of one antiviral agent over another. In addition, valacyclovir and famciclovir shows greater patient compliance than acyclovir with less frequent dosing [21]. The main benefits of administration of antiviral agents within 72 hours are to reduce the severity and duration of zoster-associated pain and the incidence of PHN [16]. Therefore, the use of antiviral agents is crucial in treatment of HZ, and should be prescribed for patients with HZ as soon as possible. In complicated cases, especially in ophthalmic zoster, disseminated zoster, or Ramsay Hunt syndrome, and in patients failing oral treatment, intravenous therapy should be considered. Many clinical trials suggest that antiviral agents should be started within 3 days of the cutaneous eruption [2224]. In general, the recommended duration of systemic antiviral agents for uncomplicated HZ is a seven-day course [17]. However, there is no solid consensus about whether it is beneficial to extend the duration of the treatment for patients with new onset vesicles after the seventh day, or for patients with either neurologic or ocular complications [21]. In herpes zoster ophthalmicus, the ophthalmic division of the fifth cranial nerve is involved, and the antiviral treatment should always be prescribed even after 3 days of the disease onset [17]. In any case of ophthalmic herpes zoster, the patient should be seen by an ophthalmologist as soon as possible, especially when vesicles on the side and tip of the nose (Hutchinson’s sign) are present. In cases with the immunosuppressed patients, antiviral therapy should always be started earlier because of the increased risk of herpes zoster complications. The same doses as in immunocompetent patients are used in immunosuppressed patients. The dosing regimen of the antiviral agents used in acute herpes zoster is summarized in Table 1. Meanwhile, the efficacy of topical antiviral agents for acute HZ had been shown to lack evidence [21].

Immunocompetent patientImmunocompromised patient
FamciclovirPO 500 mg every 8 hour for 7 daysPO 500 mg every 8 hour for 7–10 days
ValaciclovirPO 1000 mg every 8 hour for 7 daysPO 1000 mg every 8 hour for 7–10 days
AcyclovirPO 800 mg 5 times a day for 7 daysPO 800 mg 5 times a day for 7–10 days or
IV 10 mg/kg every 8 hour for 7–10 days

Table 1.

Summary of antiviral agents for treatment of acute herpes zoster.

[i] - PO, per oral, IV, intravenous.

2.2. Pain control

Since pain is the most troublesome symptom of herpes zoster, adequate pain management is the mainstream of the treatment in conjunction with antiviral therapy. Most patients require additional analgesics, although antiviral treatment may reduce the acute pain from HZ. In addition, the effective relief of acute pain may reduce the risk of progression to PHN, because severe acute pain is a risk factor for PHN. Acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioid analgesia may be used initially [25]. In patients experiencing insufficient pain relief with these agents, adjuvant analgesics such as antidepressants and anticonvulsants are shown to be effective to alleviate acute pain from HZ [24]. If parts of the pain of acute HZ may have inflammatory component, corticosteroids have been used during the acute episode of HZ. In clinical trials with selected older individuals, corticosteroids accelerate healing of the cutaneous lesion, improve quality-of-life measures, aid to return to routine activities, and reduce analgesic use. Systemic steroids starting at about 1 mg/kg/day for about 1 week, followed by 0.5 mg/kg/day for 1 week, and 0.25 mg/kg/day for another 1 week regimen is proven to be adequate to achieve these benefits [21]. If pain is refractory to formerly discussed medications, nerve block or referral to a pain specialist for sympathetic and epidural neural blockade can be performed.

3. Treatment of postherpetic neuralgia

PHN is difficult to treat and often resistant to the current pharmacologic therapies. A multimodal analgesic treatment approach should be performed achieving both the efficacy and the tolerability of the therapeutic regimen [26]. Currently, Food and Drug Administration (FDA)-approved therapies for the treatment of PHN are the transdermal lidocaine and capsaicin patches, gabapentin, and pregabalin. Therapies often use off-label or over-the-counter medications for PHN include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), opioids, antiepileptics, and nonsteroidal anti-inflammatory drugs (NSAIDs). The dosing regimen and adverse effects of treatment options for PHN are summarized in Table 2.

TreatmentRegimenAdverse effects
Topical agent
Maximum of three 5% lidocaine
patches for 12 hours a day
Itching, burning sensation or erythema
on the application site
0.025% or 0.075% capsaicin cream
8% capsaicin patch
GabapentinStarting dose of 300 mg a day to
maximum dose of 3600 mg
a day
Somnolence, dizziness,
peripheral edema
PregabalinStarting dose of 100–150 mg a day
to maximum dose of 600 mg a day
Tricyclic antidepressant (TCAs)
AmitriptylineStarting dose of 10 mg at night
to maximum dose of 100 mg at night
Dry mouth, sedation, constipation,
increased appetite, blurred vision,
tinnitus, euphoria, urinary
NortriptylineStarting dose of 10–25 mg at night
with maintenance dose of
30–75 mg a day in
divided doses
DesipramineStarting dose of 10–25 mg a day
to maximum dose of 150 mg a day
TramadolStarting dose of 50 mg every 4–6 hour
(100–400 mg a day )
MorphinePO controlled release morphine:
Starting dose of 10 mg at
night to maximum dose of 200 mg a
day or divided dose of
10–30 mg every 12 hour
IV morphine: Target dose of
0.3 mg/kg over 1 hour
to maximum dose of 25 mg with
cardiopulmonary monitoring
Nausea, vomiting, constipation,
drowsiness, dizziness, mood change,
disorientation, somnolence, headache,
OxycodonePO controlled release oxycodone:
Starting dose of 10 mg twice a day
to maximum dose of
60 mg a day
MethadoneStarting dose of 5 mg
at night escalating dosage
till dose-limiting
side effects

Table 2.

Summary of treatment options for pain management of post-herpetic neuralgia.

[i] - PO, per oral, IV, intravenous.

3.1. Pharmacological treatment

3.1.1. Topical agent

Topical application of anesthetics and analgesics may reduce pain with convenient delivery of the pharmaceutical effect, improved patient adherence, and direct access to the target site leading to decreased risk for systemic side effects. For localized and relatively mild pain, topical agents may be a reasonable choice, especially in patients who cannot tolerate systemic therapy. Currently available topical therapies include lidocaine and capsaicin patches. In addition, in a small group of patients, topical application of a cannabinoid receptor agonist resulted in pain reduction by more than 80% [27, 28]. Topical lidocaine

Lidocaine relieves pain by reducing the ectopic activity of sensory nerves. The 5% lidocaine patch has been shown in controlled clinical trials to produce significant pain relief in patients with PHN and allodynia [2932]. Often 7–10 days of treatment is required before efficacy is noted. It is easy to use and systemic toxicity is not considered a significant risk in adults. Side effects are usually limited to application site reaction, such as skin redness or rash, which may necessitate the discontinuation of treatment. Therefore, topical lidocaine is a good first-line treatment for elderly patients who have contraindications to systemic agents. The lidocaine patch contains 5% lidocaine base, adhesive, and other ingredients. In general, maximum of three patches are applied over the affected area for 12 hours a day. In addition, eutectic mixture of local anesthetics (EMLA) cream applied once a day on the affected skin with an occlusive dressing may perform as an adjuvant therapy [33]. Topical capsaicin

Capsaicin is an alkaloid derived from hot chili peppers and acts as a transient receptor potential cation channel, subfamily V, member 1 agonist that activates afferent nociceptor terminals [3436]. Topical capsaicin has proven to effectively reduce pain than placebo in patients with both musculoskeletal and neuropathic pain [37, 38]. Topical capsaicin demonstrates analgesia via a counter-irritant mechanism in which the irritation of the affected area masks the pain sensation of the skin. Also, repeated use of capsaicin results in depletion of substance P and other neuropeptides from nociceptive fibers leading to desensitization of nociceptive terminals [39]. Adverse effects are often limited to local reaction such as itching, burning sensation, soreness, and erythema at the site of application, which may slowly disappear after continued use. The systemic absorption is minimal. Application of low concentration (0.025 and 0.075%) cream formulations for several weeks have shown efficacy in neuropathic pain. An 8% capsaicin patch is also available for use in patients with PHN and HIV neuropathic pain [40, 41]. A Cochrane review in 2009 analyzed six studies treating with either a capsaicin 0.075% cream or single application of 8% patch for chronic neuropathic pain. The authors concluded that both concentrations of capsaicin may relieve pain, but there were insufficient data to prove the degree of the benefit [42].

Although topical capsaicin monotherapy is generally not considered satisfactory for patients with chronic pain, it can be helpful as an adjuvant therapy.

3.1.2. Systemic treatment

PHN is typically difficult to treat due to both unsatisfactory pain relieving effects of pharmaceuticals and dose limitations related to intolerable side effects and drug-drug interactions.

Mainly, three classes of medication are used as standard therapies to manage PHN: anticonvulsants, antidepressants (TCAs), and opioid analgesics. Anticonvulsants

Many anticonvulsants have been studied to treat chronic neuropathic pain disorders including trigeminal neuralgia and PHN. Gabapentin and pregabalin have been documented as safe and well tolerated anticonvulsant drugs helping to reduce zoster-associated pain. The mechanism of the analgesic action of gabapentin and pregabalin has not been fully described. Both gabapentin and pregabalin bind to the same receptor, α2δ subunits of voltage-gated calcium channels in the central nervous system. Since gabapentin and pregabalin are both eliminated from the systemic circulation primarily by renal excretion as unchanged drugs, the dosage of these drugs should be adjusted based on the renal function of the patients. Gabapentin

Gabapentin has been shown to be superior in relieving pain in 41–43% of patients with PHN compared to 12–23% in patients receiving placebo [43, 44]. Gabapentin is absorbed slowly and reaches a peak level at 3–4 hours after administration. Gabapentin is initiated at 300 mg daily, escalating up to 3600 mg/day as needed for pain control. Pain relief occurs as early as one week after the initiation of the treatment. Frequent adverse effects of gabapentin are somnolence, dizziness, and peripheral edema. These adverse effects are usually short-lived, but they sometimes require dose adjustment [29, 43]. Pregabalin

Pregabalin is a potent gabapentinoid and structural analog of γ-aminobutyric acid (GABA). It is an ion channel modulator that has rapid analgesic, anticonvulsive, and anxiolytic effects. Pregabalin has been shown to relieve pain by more than 50% in 50% of patients with PHN compared to 20% in placebo groups [45, 46]. Dizziness, somnolence, and peripheral edema were also the most often reported adverse effects for pregabalin, although pregabalin usually has fewer dose-related adverse events than gabapentin because of the lower doses used [4547]. Pregabalin has improved pharmacokinetics with better absorption and steadier blood levels and a faster onset of action than gabapentin. Therefore, titration of pregabalin to the therapeutic dose range is more rapid [47]. Pregabalin can be given in two divided doses per day, offering greater convenience than gabapentin [47, 48]. In general, the starting dose is 100–150 mg/day in divided doses escalating to 300 mg/day within one week, considering tolerability and effectiveness. Further up regulation of the dose up to 600 mg/day in 2–4 weeks may be considered for patients who experience unsatisfactory effect. Tricyclic antidepressant

The TCAs work by blocking neuronal uptake of noradrenaline and serotonin, thereby potentiating inhibition of spinal neurons involved in nociceptive perception. Since the TCAs also block α-adrenergic receptors and sodium channels, they are known to be useful in PHN in which damaged primary afferent neurons develop adrenergic sensitivity and generate ectopic impulses closely related to sodium-channel blockade. In several randomized, controlled trials, the TCAs have been shown to relieve pain in 44–67% of elderly patients with PHN [26, 4951].

The reported adverse effects of the TCAs include excessive sedation, cognitive impairment, dry mouth, constipation, sexual dysfunction, and orthostatic dizziness. The contraindications of the TCAs are patients with cardiovascular disease, glaucoma, and urinary retention. In addition, the patients with high risk of suicide are administered with caution. In general, the starting dose of TCAs is 10–25 mg/night for elderly patients. The dose may be increased by 25 mg nightly up to maximal dose. TCAs such as amitriptyline, nortriptyline, desipramine are well studied and documented as effective managements of PHN. Amitriptyline

Amitriptyline is a tricyclic antidepressant that is widely used to treat various chronic neuropathic pains including PHN. However, there is insufficient evidence to recommend amitriptyline as a first-line agent for neuropathic pain with an overestimation of treatment effect. A Cochrane review in 2015 analyzed 17 studies involving 1342 oral amitriptyline-treated participants. The authors concluded that amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief [52]. Amitriptyline is started at a low dose of 10 mg/night, with gradual dose increase up to 100 mg/night [11]. Nortriptyline

Nortriptyline, along with desipramine, is a preferred alternative treatment to amitriptyline because of its lesser adverse effects for the elderly such as cardiac problems, sedation, cognitive impairment, orthostatic hypotension, and constipation [53]. A recent Cochrane review in 2015 analyzed six studies treating 310 participants with various neuropathic pain conditions. The authors concluded that little evidence supports the use of nortriptyline as effective treatment for neuropathic pain [54]. The starting dose is 10–25 mg/night and the dosage may be increased by 25 mg/day with 1 week interval. In general, maintenance dose is 30–75 mg daily in divided doses, or a single night dose [11]. The most common side effects include dry mouth, sedation, constipation, increased appetite, mild blurred vision, tinnitus, and often euphoria and mania [55].

In a double-blind, randomized controlled trials, patients with diabetic polyneuropathy or PHN were randomized to receive nortriptyline and gabapentin, alone or in combination [56]. Combination regimen of gabapentin and nortriptyline produced greater pain relief than either agent alone. Therefore, combination therapy may benefit patients with PHN, but with higher risk of adverse effects than with either drug alone. Desipramine

A Cochrane review in 2014 analyzed five studies treating 177 participants with painful diabetic neuropathy or PHN. The authors concluded that this review found little evidence to support the use of desipramine as effective treatment for neuropathic pain, although there was very low quality evidence of benefit and harm [57]. In randomized, placebo-controlled, double-blind, crossover studies, amitriptyline and desipramine have been shown to be effective for the treatment of PHN [58, 59]. Results from these studies showed that 67% of patients taking amitriptyline rated their pain relief as good to excellent, and 63% of patients taking desipramine rated their pain relief as moderate or better. Typically, the initial dose of desipramine for treatment of PHN is 10–25 mg/day with a maximum dose of 150 mg/day [11]. Opioid analgesics

Pain management with opioids may also alleviate PHN. Although effective in treating PHN, the issue of tolerance and concerns of misuse and abuse often tends to prevent opioids from being used as first-line agents. Opioids regulate pain binding to the opioid receptors such as μ, κ, δ and nociceptors present in both central and peripheral nervous system. The opioid receptors are activated by binding to inhibitory G-proteins, resulting in closure of voltage-gated calcium channels. This process leads to a cascade of potassium efflux causing hyperpolarization and reduced cyclic adenosine monophosphate level, hence decreasing the neuronal excitability. Additionally, opioids are capable of diverse and complex pharmacologic effects because they may function with various potencies acting as an agonist, partial agonist, or an antagonist binding to more than one receptor subtype. Side effects of opioids include constipation, cardiorespiratory dysfunction, sedation, nausea/vomiting, and histamine release [11]. Since constipation is a major side effect in elderly persons, bulk laxatives should be recommended. Additionally, the fact that many patients with PHN are elderly and have other underlying diseases for which they are taking medication emphasizes the need for close monitoring of adverse effects [11, 30, 60]. Tramadol

Tramadol is a synthetic 4-phenyl-piperidine analogue of codeine and acts as an analgesic with both opioid and non-opioid analgesic activity. Besides the opioid analgesic activity, it works via inhibition of noradrenaline reuptake and stimulation of serotonin release at the spinal level. Thus, it has properties of both an opioid and a TCA. In a randomized clinical trial, tramadol was proven to be an agent that significantly improve quality of life and alleviate pain in patients with PHN [61]. Adverse effects of tramadol include nausea, vomiting, constipation, drowsiness, dizziness, somnolence, headache, and seizures. Concomitant use of SSRIs, selective serotonin-and norepinephrine-reuptake inhibitor (SSNRIs), or TCAs should be avoided and drug interactions should be monitored [24]. It is generally dosed at 100–400 mg/day, in divided doses. The starting dose is 50 mg every 4–6 hours [26, 49]. Morphine

In a crossover trial with patients suffering PHN, both controlled release morphine and TCAs provided significant pain relief compared to placebo group [62]. In this report, patients preferred treatment with opioid analgesics to either TCAs or placebo, despite a higher incidence of adverse effects and more dropout patients during opioid treatment. In another crossover trial, patients with diabetic polyneuropathy or PHN were randomized to daily active placebo, sustained-release morphine, gabapentin, and a combination of gabapentin and morphine [63]. Combination regimen with morphine and gabapentin showed superior effect in pain relief than either agent alone or the active placebo, but with increased adverse effects. The starting dose of oral controlled release morphine is 10 mg/night and the dose is increased twice weekly till maximal dose of 200 mg/day. Also, it can be given at divided dose of 10–30 mg every 12 hours as needed [62]. For intravenous morphine, the target dose is 0.3 mg/kg over 1 hour, up to a maximum of 25 mg with cardiorespiratory monitoring in inpatient setting [64]. The adverse effects include nausea, vomiting, constipation, drowsiness, dizziness, mood change, and disorientation [26, 49]. Oxycodone

A Cochrane review in 2014 analyzed three studies treating 254 participants with painful diabetic neuropathy or PHN. In all three studies, controlled release oxycodone was used with doses titrated up to a maximum of 60–120 mg daily. The authors concluded that no convincing, unbiased evidence suggesting oxycodone is of value in treating patients with painful diabetic neuropathy or PHN exists [65]. However, other randomized, placebo-controlled crossover trials suggest greater efficacy of controlled release oxycodone over placebo [66]. The dose is 10 mg twice daily, up to a maximum of 60 mg/day. Adverse effects are typical of other opioids [30]. Methadone

Methadone is a synthetic opioid agonist that exhibits a potent antagonist effect on glutamate N-methyl-D-aspartate (NMDA) receptors. Although there is a great paucity of clinical evidence regarding the treatment effect of methadone on PHN, methadone may be tried as an adjunctive treatment for PHN. In a recent double blind and placebo controlled study, methadone, when compared to placebo, did not significantly affect the intensity of spontaneous pain, as measured by the visual analogue scale [67]. However, the intensity of spontaneous pain was significantly decreased after the methadone treatment, compared to placebo by the category verbal scale (50% improved after the methadone treatment, none after the placebo, p=0.031). Evoked pain was reduced under methadone compared to placebo (50% improved after the methadone treatment, none after the placebo, p=0.031). The starting dose is 5 mg/night and is increased till maximal pain relief is achieved or occurrence of dose-limiting side effects. Methadone has a high intestinal absorption, and most of the drug is excreted in feces with no significant renal elimination, hence this drug is safe for patients with renal failure [68].

3.2. Non-pharmacological treatment

As a general rule, non-pharmacological, interventional pain management is frequently used in acute settings or in patients who have failed the standard therapies.

3.2.1. Nerve block

The interventional treatments including sublesional anesthesia, epidural blocks, intrathecal injection, and sympathetic nerve blocks with and without corticosteroids have been reported in large series, but rarely studied in a controlled manner. They have limited evidence of effective treatment of PHN [29]. Epidural block with local anesthetics and steroids is not effective in providing long-term pain relief in patients with PHN. Sympathetic nerve blocks have shown beneficial effects in patients with acute HZ, but with insufficient effect in providing long-term pain alleviation in patients with PHN [69]. Long-term pain relief by peripheral nerve block using local anesthetics has been reported, but with limited quality of the evidence [70].

3.2.2. Spinal cord stimulation

Spinal cord stimulation (SCS) has been used for the management of chronic neuropathic pain disorders [71, 72]. However, no randomized controlled study supports the usefulness of SCS. Studies on SCS were all case series with a small number of cases [7375]. Therefore, SCS should be used only as a next resort after intrathecal steroid injections or nerve blocks in patient’s refractory to pharmacological treatments of PHN.

3.2.3. Transcutaneous electrical nerve stimulation

Transcutaneous electrical nerve stimulation (TENS) is the use of electric current produced by a device to stimulate the nerves at a strong but nonpainful intensity that can produce pain relief [76]. TENS is an adjunctive therapy that has shown efficacy in transiently relieving neuropathic pain [77, 78]. In a study of TENS for patients with chronic pain, approximately 30% of patients with PHN fail to respond to TENS and among patients who respond initially, only a third continue to obtain pain relief after 2 years [77]. In a recent pilot randomized study of patients who were refractory to previous pharmacological therapy, the patients were treated with TENS with a biofeedback capability [79]. After every two treatments with the sham and true device, the patients were required to fill out a standard neuropathic pain scale score. The patients had choices to select the other device after three consecutive treatments if they felt an insufficient relief in their pain. The true device was chosen over the sham device by all patients. The majority of these patients treated by the true device reported a significant decrease in pain scores.

3.2.4. Botulinum toxin

BTX-A may play an adjunctive role as a promising therapeutic modality for PHN with its proven efficacy, safety, and tolerability. Botulinum toxin A (BTX-A) blocks acetylcholine by cleaving synaptosomal-associated protein of 25 kDa (SNAP25), which participates in the formation of the exocytic soluble N-ethylmaleimide–sensitive factor attachment protein receptor complex(SNARE) that is essential for the fusion of acetylocholine-containing vesicles with the presynaptic membrane [80, 81]. Therefore, the local peripheral BTX-A injection may result in anti-nociceptive effect associated with the inhibition of formalin-induced glutamate release, substance P and calcitonin gene–related peptide, which participates in the neurogenic inflammation [82]. There are several case series and randomized controlled trials supporting both therapeutic benefit and safety of BTX-A on PHN patients [8388]. In these studies, no significant safety issues including local or systemic adverse effects was raised except the pain during injections. A possible consideration to BTX-A use is that, unlike other therapeutic modalities for PHN, it may induce antitoxin antibodies that could probably limit the long-term repetitive use of the treatment [89].

4. Vaccination against herpes zoster

In a randomized trial with elderly patients, adult vaccination reduced the incidence of herpes zoster by 51% and the incidence of postherpetic neuralgia by 66%. In patients 70 years of age or older as compared with patients 60 to 69 years of age, the vaccine was less effective in reducing the risk of herpes zoster (38% reduction) but demonstrated similar protection against PHN (67% reduction) [90]. A live attenuated VZV vaccine has been available since 2006. It is a one-dose, high-potency vaccine originally approved for immunocompetent persons 60 years of age or older, but in 2011, it was approved to include persons aged 50–59 years [91]. This live attenuated vaccine is contraindicated in pregnant women and immunocompromised individuals. The reported side effects of the vaccine are minor, such as erythema, pain, and an itching sensation at the injection site, and fever [90]. Regarding the persistence of vaccine efficacy, the Shingles Prevention Study demonstrated the proven efficacy of the vaccine through four years post-vaccination. Additionally, the Short-Term Persistence Substudy subsequently demonstrated the persistence of vaccine efficacy through five years post-vaccination, although the efficacy beyond five years is uncertain [92]. Overall, the zoster vaccination can be used as the first line management for the prevention of HZ and PHN.

5. Conclusion

As the general population ages, the number of patients suffering from HZ and PHN may increase gradually in the future. Diverse and comprehensive efforts are necessary as patients suffering from acute HZ and PHN are burdened by a worse quality of life due to both physical and psychological impairments [11]. We summarized the management of acute HZ and PHN to shorten the duration and intensity of pain. In order to choose the optimal treatment, clinicians should consider issues related to efficacy, safety, and tolerability in conjunction with individuals’ goals of therapy, preferences, and adherence issues. Finally, regardless of the agents chosen, the adverse effects and drug interactions should always be considered to provide safe and effective management of pain.


This work was supported by the Basic Science Research program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (2015R1C1A2A01055073).


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