Analgesic options for herpes pain vary depending on the degree of pain. The modalities for managing herpes pain can be divided into acute therapy and postherpetic neuralgia therapy.

Medications for Acute and Postherpetic Neuralgia Pain
Thoracic Herpetic Rash

Herpes Zoster or Shingles is a disease caused by reactivation of the varicella-zoster virus acquired from the previous primary varicella infection exposure. The factor that can trigger this virus's reactivation is the decreased immunity ( such as HIV, chemotherapy, malignancy, or long-term use of corticosteroids).

Reactivation of the varicella-zoster virus from the dorsal root ganglia will produce a herpetiform rash that spreads along the dermatome line with pain. The pain can be felt like a burning sensation lasting several days to several months, even though the rash has disappeared (postherpetic neuralgia).


Herpetic Pain Managements


a. Acute Pain Management

Acute pain therapy in herpes zoster aims to reduce the severity of the rash, the infectious period, and the risk of developing postherpetic neuralgia (PHN).

Anti Virus
Initially, antivirals were used to speed up the process of getting rid of the rash. However, some studies show that antivirals are also useful in reducing pain intensity and preventing postherpetic neuralgia (PHN).

A 2004 RCT conducted a study in 55 patients to compare acyclovir administration with famciclovir to uncomplicated herpes zoster. The study results mentioned that administration of famciclovir 3 x 250 mg daily was as effective as taking 5x800mg of acyclovir in accelerating the duration of rash relief and reducing pain intensity.

However, a Cochrane review in 2014 stated that administering oral antivirals did not affect reducing pain intensity or preventing PHN.

Corticosteroids
Corticosteroids are given to patients with shingles as an adjunct therapy. Prednisone is a corticosteroid that is usually given together with acyclovir because it is believed to reduce pain by reducing the degree of neuritis caused by the infection and reducing damage to the affected nerves.

A small sample clinical trial compared the administration of valacyclovir alone, the valacyclovir-pregabalin combination, and the valacyclovir-pregabalin-methylprednisolone combination. The study results showed that persistent pain was more prevalent in the group that was given only 1x1 gram of valacyclovir for seven days and the valacyclovir-pregabalin group, compared to the group that received the combination valacyclovir-pregabalin-methylprednisolone for seven days. Methylprednisolone is given in a dose of 0.64 mg/kg weight/day divided into 2 doses.

A Cochrane review in 2013 stated that scientific evidence of moderate quality does not support the acute administration of corticosteroids in herpes zoster. Short-term administration of corticosteroids has not been shown to effectively reduce pain intensity nor prevent PHN.

Analgesics
Herpes zoster with mild to moderate pain can often be treated with non-narcotic analgesics or antipyretics such as paracetamol and NSAIDs (nonsteroidal anti-inflammatory drugs) that can also be combined with tramadol. In moderate or severe pain, scheduled opioid administration using oxycodone or morphine is required.

If the pain is not resolved, nortriptyline, pregabalin, or gabapentin can be used. However, these three drugs' role in reducing the intensity of acute herpes zoster pain is still not supported by much scientific evidence.


b. Postherpetic Neuralgia Pain Managements

Postherpetic neuralgia (PHN) is chronic neuropathic pain that lasts for at least one month in infected neurological pathways, with an onset of between one and six months after the skin rash improves and can last for years.

Pain in PHN can be divided into three stages, namely acute, subacute, and chronic pain. Acute pain is pain that appears within 30 days of the appearance of the skin rash. Subacute pain persists after the acute phase has passed but gets better before the diagnosis of upright PHN. The chronic pain stage is the PHN itself, which lasts for 120 days or more after the skin rash.

The first-line medications for treating PHN are tricyclic antidepressants (especially amitriptyline), anticonvulsant drugs (such as gabapentin and pregabalin), and topical anesthetics. The second-line drugs are opioids and capsaicin.

Tricyclic Antidepressants
Low-dose tricyclic antidepressants are widely used as pharmacotherapy for PHN, either as monotherapy or in combination with other analgesics. The action of antidepressants is through the reuptake blockade of serotonin and norepinephrine and inhibition of voltage-dependent sodium channels. Amitriptyline is the most widely used drug.

Common side effects include dry mouth, blurred eyes, dizziness, fatigue, drowsiness, urinary retention, constipation, weight gain, palpitations, orthostatic hypotension, and prolonged QT interval.

An RCT, conducted in 49 patients with postherpetic neuralgia, compared the administration of amitriptyline, a combination of amitriptyline and fluphenazine, fluphenazine, and placebo. The results showed that the administration of amitriptyline for eight weeks gave significant results in reducing patient pain.

However, a Cochrane review mentioned that only 1/3 of patients taking tricyclic antidepressants for neuropathic pain experience moderate pain symptom improvement. Also, there is no scientific evidence to support the use of other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), in the management of neuropathic pain.

Anticonvulsants
Anticonvulsant drugs are also often given to patients with neuropathic pain, namely gabapentin and pregabalin. Both drugs are gamma-aminobutyric acid (GABA) analogs.

A clinical trial in 2005 stated that giving gabapentin 1 x 900 mg can reduce pain in cases of shingles by 66% compared to 33% in giving a placebo.

Side effects of gabapentin include drowsiness, dizziness, ataxia, and peripheral edema. Low-dose gabapentin, when combined with low-dose opioids, will provide better analgesia than either drug used as monotherapy at a therapeutic dose.

Pregabalin is a relatively safe drug of choice for PHN management because it can control pain effectively and has very little interaction with other drugs. The side effects of pregabalin are generally mild and include peripheral edema.

Another anticonvulsant that can be used in the treatment of PHN is carbamazepine. This drug acts as a sodium channel antagonist, as well as a pre-and post-synaptic neuronal membrane stabilizer. Carbamazepine is effective in paroxysmal and excruciating pain but less effective in burning pain and allodynia.

Common side effects are dizziness, blurred vision, nausea, and vomiting. A reddish rash is also common, but this rarely progresses to Steven Johnson syndrome or toxic epidermal necrolysis.

Lidocaine
A clinical trial in 2008 conducted a study on 46 patients with herpes zoster infection who complained of moderate to severe pain and compared the administration of a 5% lidocaine patch with a placebo. This study found that administering a patch measuring 10 cm x 14 cm, containing 700 mg of aqueous-based lidocaine, could benefit the management of herpes pain. However, this study has the drawback that oral analgesics were also administered to the study subjects, so there is a bias.

Lidocaine works by inhibiting sodium channels and reducing abnormal ectopic discharge. Currently, lidocaine is available in topical preparations in the form of skin patches and creams. Topical lidocaine is effective and safe for PHN, with a low incidence of side effects and systemic adverse events.

Opioids
Opioids are effective in the management of neuropathic pain, especially in moderate to severe neuropathic pain. However, its use should consider dose titration to minimize side effects and prevent tolerance and abuse. Common side effects include nausea, vomiting, obstipation, dizziness, and drowsiness. The recommended opioids for PHN are morphine and oxycodone.

Capsaicin
Capsaicin can relieve neuropathic pain induced by sensitization of the peripheral substance P of the main afferent fibers (C / C fibers). This drug will stimulate the release of substance P in the periphery so that all substance P deplete stores. The absence of substance P causes no pain induced by substance P in the main afferent fibers.

A Cochrane review states that the use of high concentrations of capsaicin effectively reduces the degree of pain. However, the quality of available scientific evidence is still low. Further studies are still needed in this regard.

Capsaicin is available in a topical form (transdermal patch) and can be applied to the skin for 30-60 minutes. This medicine should not be used on areas of skin that have been injured.



Conclusion
The pain management options in herpes zoster can be divided into two, namely acute pain management and postherpetic neuralgia (PHN) management.

The use of antivirals in acute pain has been reported to accelerate the rash's disappearance, reduce the degree of pain, and prevent postherpetic neuralgia. However, a Cochrane review reports results that do not support this.

Corticosteroids are also frequently used as an adjunct to the management of acute shingles pain. Still, a Cochrane review suggests that short-term administration of corticosteroids is not effective in reducing pain intensity or preventing PHN.

The administration of analgesics for acute pain management in herpes zoster depends on the degree of pain. Mild-moderate pain can be managed with paracetamol, nonsteroidal anti-inflammatory drugs, or in combination with tramadol. For moderate to severe pain, morphine or oxycodone can be given.

Tricyclic antidepressants are often used to treat PHN, but this is not supported by existing scientific evidence. Treatments that can be used for PHN are anticonvulsants, topical lidocaine, and capsaicin.