Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (shingles). It produces chronic pain along cutaneous nerves and often some distortion of sensation. The pain can either persist after the acute episode of shingles or recur in an area previously affected by shingles. See also separate Shingles and Shingles Vaccination article.
- There are various definitions for PHN with regards to time of onset and duration of pain. This makes estimates about its prevalence difficult.
- The incidence in UK primary care is thought to be about 3 per 1,000 person-years.
- In England and Wales there are thought to be 225,000 new cases per year.
- Herpes zoster infection occurs in around 30% of people aged over 70.
- Approximately 20% of people will experience PHN after the initial rash has cleared.
- It is uncommon in children.
- The virus remains dormant in the nerve cell bodies of the asymptomatic host after an initial infection with varicella-zoster virus.
- It can also become latent in the satellite cells of the dorsal root, cranial nerves or autonomic ganglia.
- Reactivation of the latent herpes virus occurs in around 50% of people. It is more common in older people.
- Pain from acute herpetic neuralgia typically lasts 3-5 weeks.
- There is some evidence that a low-grade ganglionitis is responsible for PHN developing.
Factors that may predispose to PHN include:
- Older age (>50 years).
- The incidence of PHN has been shown to rise from 8% at 50-54 years of age to 21% at 80-84 years of age.
- Female sex.
- Patients with severe immunosuppression and diabetes mellitus.
- Presence of severe pain during the attack of shingles.
- A more extensive and severe rash from shingles, especially if it extends beyond one dermatome.
- The presence of a prodrome (48-72 hours of throbbing pain and paraesthesia in the region of the affected sensory nerve before the shingles rash develops).
- The site of the herpes lesion:
- Risk of PHN is low in the jaw, neck, sacral, and lumbar regions.
- Risk is moderate in the thoracic area.
- The highest risk is in the trigeminal area, especially the ophthalmic division, and also the brachial plexus.
- Herpes zoster presents initially with a painful vesicular eruption in a single dermatome.
- The eruption resolves but in PHN, pain continues.
- PHN is often defined as a chronic neuropathic pain condition that persists three months or more following an outbreak of shingles.
- Pain is intense and may be described as burning, stabbing, shooting or throbbing.
- The affected area may be itchy.
- There may be allodynia: pain is produced by stimuli that are not usually painful - eg, a cold draught or heat, or light touch.
- Hyperalgesia may be present: there is increased sensitivity to painful stimuli.
- Pain can be debilitating. It can interfere with activities of daily living, and can also be so severe that it leads to depression and social isolation.
- Insomnia is very common and occurs more frequently in those with more severe pain.
- Symptoms may be present for a few months or even years.
- The area affected by shingles may show some scarring.
- There may be either hypersensitivity or reduced sensation in affected areas.
- Allodynia may be demonstrated.
The diagnosis is usually clinical and no specific investigations are indicated.
- Explain the nature of the condition to the patient, including expected duration of symptoms and aims of treatment.
- Advise the patient to wear loose clothing and, next to the skin, cotton. This will cause less irritation.
- Cling film or a plastic wound dressing may help to protect sensitive areas.
- Cold packs may help to ease pain (unless there is associated allodynia made worse by cold).
- Start with paracetamol or a paracetamol/codeine combination.
- There is no evidence to support the use of non-steroidal anti-inflammatory drugs (NSAIDs) for patients with PHN.
- Management should consider reducing the impact of pain on quality of sleep as well as overall pain reduction.
- The considerable side-effect profiles of the commonly used oral medications often limit their practical use. A combination of both topical and systemic agents may be required for optimal outcomes.
- If there is severe pain at the outset or if the above measures are not sufficient, add in either a tricyclic antidepressant (off-licence) or gabapentin (licensed) which have been shown to be effective in the treatment of PHN:
- Tricyclic antidepressants:
- Amitriptyline (most widely used) or nortriptyline may be used.
- Care should be taken, especially in the elderly, due to the possibility of anticholinergic side-effects which can lead to acute confusion or cardiac arrhythmias.
- Initial dose of amitriptyline is 25 mg at night (10 mg if elderly/frail) and 10 mg of nortriptyline.
- Increase by weekly increments of 25 mg (10 mg if elderly/frail) for amitriptyline and 10 mg for nortriptyline until pain is controlled or side-effects occur.
- Maximum dose is 75 mg at night (50 mg if elderly/frail) for amitriptyline and 100 mg for nortriptyline.
- One study showed that giving amitriptyline 25 mg nocte for 25 days reduced the incidence of PHN from 33% to 16%.
- Use of tricyclic antidepressants is often limited by their side-effects.
- Anticonvulsant treatments:
- Both gabapentin and pregabalin have been shown to reduce pain and improve sleep patterns in patients with PHN.
- Gabapentin can be started with 300 mg once daily on day one, 300 mg twice daily on day two, and 300 mg three times daily on day three.
- Then increase the dose by 300 mg daily every two to three days according to the response.
- Maximum dose is 3600 mg. This dose should be achieved over a minimum period of three weeks.
- Slower titration may be needed for patients such as the elderly or frail. A single bedtime dose of 100 mg can be given to elderly frail patients.
- Pregabalin 75 mg bd can be given (to a maximum of 300 mg bd) if there are side-effects, such as sedation or ataxia, with gabapentin.
- Tricyclic antidepressants:
- Strong opioids can provide similar pain relief to tricyclic antidepressants but can be associated with more side-effects.
- Topical capsaicin (0.075%) patch can be used topically if other treatments have not worked, are not appropriate or at a patient's request.The skin needs to have healed completely. There can sometimes be a four-week delay before benefit is felt.
- If patients experience a burning sensation with topical capsaicin then the cream can be mixed with either glyceryl trinitrate (GTN) paste or Emla® cream.
- Topical lidocaine 5% patches can be considered if oral or other topical treatment is not suitable or is not tolerated. They are not recommended as first-line treatment. They should be applied for 12 hours and then removed for 12 hours.
- The 5% lidocaine medicated plaster has been shown to be as effective as systemic pregabalin in PHN but with an improved tolerability profile.It also provides benefits beyond pain relief such as improving quality of sleep.
- There is some evidence that botulinum toxin treatment is effective in managing PHN.
When to refer to a specialist pain clinic
- If the above treatment does not control pain after four to six weeks.
- Patients with severe pain.
- Patients whose quality of life is being affected.
- There are adverse effects of medication that are affecting/limiting treatment.
- Additional treatment such as perineural local anaesthetic injections, transcutaneous electrical nerve stimulation (TENS) and psychological coping strategies may be considered.
- Most patients with PHN will experience a slow improvement over a long period of time, particularly when medical management is used.
- There is a small group failing to show any improvement despite medical treatment.
- No treatment has been shown to prevent PHN completely.
- Placebo-controlled trials of antiviral drugs for acute herpes zoster have shown that they reduce the severity of acute pain and rash, hasten rash resolution and reduce the duration of pain.
- However, a Cochrane review has stated that there is high-quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments.
- There is no evidence that prescribing oral steroids, either alone or with antivirals, actually reduces the risk of developing PHN.
- The only well-documented means of preventing PHN is the prevention of herpes zoster.
- Vaccination is the most effective way to prevent the occurrence of herpes zoster complications in the elderly, in particular PHN:
- Studies have shown that giving older people (adults aged over 60) varicella-zoster vaccine boosts their waning immunity and reduces their risk of developing PHN.See separate Shingles and Shingles Vaccination article.
- The vaccine is safe and well tolerated.
- A universal vaccination programme for those aged 70-79 was introduced from September 2013.
Further reading and references
Pinchinat S, Cebrian-Cuenca AM, Bricout H, et al; Similar herpes zoster incidence across Europe: results from a systematic literature review. BMC Infect Dis. 2013 Apr 1013(1):170.
Belmin J, Jarzebowski W, Lafuente-Lafuente C; Zoster and postherpetic neuralgia: vaccine prevention is available. Geriatr Psychol Neuropsychiatr Vieil. 2015 Sep 113(S2):15-20.
Mehta N, Bucior I, Bujanover S, et al; Relationship between pain relief, reduction in pain-associated sleep interference, and overall impression of improvement in patients with postherpetic neuralgia treated with extended-release gabapentin. Health Qual Life Outcomes. 2016 Apr 114(1):54. doi: 10.1186/s12955-016-0456-0.
Forbes HJ, Thomas SL, Smeeth L, et al; A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain. 2016 Jan157(1):30-54. doi: 10.1097/j.pain.0000000000000307.
Hadley GR, Gayle JA, Ripoll J, et al; Post-herpetic Neuralgia: a Review. Curr Pain Headache Rep. 2016 Mar20(3):17. doi: 10.1007/s11916-016-0548-x.
Lee DH, Park JE, Yoon DM, et al; Factors Associated with Increased Risk for Clinical Insomnia in Patients with Postherpetic Neuralgia: A Retrospective Cross-Sectional Study. Pain Med. 2016 Apr 12. pii: pnw066.
Moore RA, Derry S, Aldington D, et al; Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Jul 67:CD008242. doi: 10.1002/14651858.CD008242.pub3.
Moore RA, Wiffen PJ, Derry S, et al; Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014 Apr 274:CD007938. doi: 10.1002/14651858.CD007938.pub3.
Neuropathic pain – pharmacological management: The pharmacological management of neuropathic pain in adults in non-specialist settings; NICE Clinical Guideline (November 2013, updated April 2018)
Burness CB, McCormack PL; Capsaicin 8% Patch: A Review in Peripheral Neuropathic Pain. Drugs. 2016 Jan76(1):123-34. doi: 10.1007/s40265-015-0520-9.
de Leon-Casasola OA, Mayoral V; The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence. J Pain Res. 2016 Feb 129:67-79. doi: 10.2147/JPR.S99231. eCollection 2016.
Binder A, Rogers P, Hans G, et al; Impact of topical 5% lidocaine-medicated plasters on sleep and quality of life in patients with postherpetic neuralgia. Pain Manag. 2016 Jan 28.
Mittal SO, Safarpour D, Jabbari B; Botulinum Toxin Treatment of Neuropathic Pain. Semin Neurol. 2016 Feb36(1):73-83. doi: 10.1055/s-0036-1571953. Epub 2016 Feb 11.
Johnson RW, Rice AS; Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16371(16):1526-33. doi: 10.1056/NEJMcp1403062.
Chen N, Li Q, Yang J, et al; Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2014 Feb 62:CD006866. doi: 10.1002/14651858.CD006866.pub3.
Langan SM, Smeeth L, Margolis DJ, et al; Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLoS Med. 201310(4):e1001420. doi: 10.1371/journal.pmed.1001420. Epub 2013 Apr 9.
Millions more protected against disease through improved vaccination programme; Dept of Health, April 2013