Postherpetic Neuralgia


Postherpetic neuralgia (PHN) is a neuropathic pain syndrome that occurs following an acute episode of herpes zoster, commonly known as shingles . As with other manifestations of neuropathic pain, the pain of PHN is caused by a lesion of the somatosensory pathway of the nervous system. The management of neuropathic pain conditions such as PHN is often challenging as many patients have an inadequate response to treatment. Although pharmacologic and other noninvasive therapies are typically tried first, interventional treatments may be considered for refractory cases.

PHN is the most common complication of herpes zoster infection. Acute herpes zoster (AHZ) results from the reactivation of the latent varicella-zoster virus (VZV) and is characterized by a painful skin rash that involves the dermatome innervated by the affected sensory ganglion. PHN manifests as pain that persists in the same area as the herpes zoster rash following resolution of the rash. The most common definition refers to PHN as pain that persists for more than 3 months; however, this is an arbitrary distinction and other definitions include neuralgia ranging from 1to 6 months after rash onset. Pain associated with this condition can last for months to years after healing of the rash.

There are approximately one million cases of AHZ annually in the United States, and one in three individuals will develop AHZ in their lifetime. The frequency and severity of PHN increases with age. The incidence of PHN in patients with AHZ increases from 5% in individuals younger than 60%–20% in those 80 years or older ( Fig. 20.1 ). Aside from advanced age, risk factors for the development of PHN following an episode of AHZ include prodromal sensory symptoms (pain or abnormal sensations before the onset of the rash), severe rash, immune compromise, and greater acute pain. ,

Fig. 20.1

Percentage of patients with herpes zoster developing PHN by age group.

Source: Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc . 2007;82(11):1341–1349.

Etiology and Pathogenesis

VZV, a double-stranded herpes virus, is the causative agent of herpes zoster. Primary infection with VZV results in varicella ( chickenpox ), typically seen in childhood. The virus subsequently lies dormant in the sensory ganglion following the resolution of the infection. Impairment of cellular immunity, as occurs with increasing age or immunosuppression, allows for reactivation of the virus. VZV reactivation results in viral particle migration from the sensory ganglion to the dorsal horn of the spinal cord and to the surface of the skin. This process is accompanied by an immune response and inflammation.

The pathophysiology of PHN is complex and involves central and peripheral nerve injury. Viral reactivation and propagation lead to changes in the processing of central nervous system signals and peripheral nerve damage. , , These damaged peripheral neurons generate spontaneous discharges and develop a lowered action potential threshold, resulting in exaggerated responses to stimuli. , Similarly, central nerve injury leads to an augmented response to nociceptor input.

Clinical Features

Herpes zoster develops as a unilateral, erythematous papular rash that in many instances affects a single dermatome, or occasionally two contiguous dermatomes. Frequently affected dermatomes include the cervical, mid-to-lower thoracic, and trigeminal regions. , Pain associated with AHZ precedes the onset of the rash and typically lasts 2–4 weeks. The rash evolves into grouped vesicles, which subsequently form pustules that ulcerate and form scabs. The rash typically lasts 7–10 days, though complete healing may take up to 4 weeks. Scarring and changes in pigmentation may be seen after the healing of the rash. Although the pain of AHZ resolves for most individuals, approximately 10% of patients develop PHN. ,

Patients with PHN may report one or more of the following patterns of pain: constant burning or aching pain, intermittent lancinating or shock-like pain, and pain provoked by a normally nonpainful stimulus (allodynia) or disproportionate pain to a noxious stimulus (hyperalgesia). , , Approximately 90% of patients have allodynia. , Patients frequently exhibit sensory deficits in the affected area, particularly loss of tactile, pinprick, and thermal sensation. ,

The physical and psychosocial aspects of life may be disrupted in individuals suffering from PHN. Patients may exhibit impaired appetite, sleep disturbances, depression, diminished libido, and decreased energy levels. Patients also report decreased quality of life and interference with their activities of daily living due to the pain. ,


The diagnosis of PHN is based on clinical presentation, and thus a thorough medical history and physical examination is essential. Routine history taking should include the patient’s symptoms and quality of the pain, vaccination history, and impact of pain on daily life. The Zoster Brief Pain Inventory is a validated tool that can be used to assist in the assessment of pain and discomfort for patients with PHN.

PHN diagnosis is usually straightforward as it is usually pain that persists for over 3 months in the same affected area as the episode of AHZ. However, diagnosis may be more difficult if the rash resolves or if the patient does not remember the rash. Consideration of PHN risk factors—including older age, severe rash, severe pain with AHZ, and localization to the trigeminal or brachial plexus dermatomes—may also aid in diagnosis.

Laboratory tests are not typically needed for the diagnosis of PHN. Rarely, the neuropathic pain of AHZ can occur in the absence of a rash ( zoster sine herpete ). The diagnosis of this condition may require the detection of VZV DNA in cerebrospinal fluid. ,

Differential Diagnosis

Patient history and clinical findings may help to differentiate herpes zoster from other skin conditions and PHN from other neuropathies and pain syndromes. Herpes zoster can be mistaken for impetigo, candidiasis, herpes simplex virus, contact dermatitis, drug-related eruptions, insect bites, autoimmune blistering disease, and dermatitis herpetiformis. , The differential diagnosis of PHN includes trigeminal neuralgia, migraine headache, cluster headache, peripheral neuropathy, paroxysmal hemicrania, nerve tumor, and traumatic nerve injury.

Physical Exam Findings

A physical examination should include a comparison of the sensory findings on the affected side to that of the contralateral side. , The affected area may display hyperalgesia and allodynia upon application of mechanical or thermal stimuli. , In some patients, the involved dermatome(s) may also demonstrate decreased sensation to temperature, touch, and pinprick. Scarring may be identified on exam due to the cutaneous changes related to the episode of AHZ. Changes in autonomic function including increased sweating may also be present on physical exam.


There is no single therapy that reliably alleviates PHN. PHN is most effectively treated with a multimodal analgesic approach that utilizes multiple therapies with different mechanisms of action. Treatment can include a range of therapies including systemic medications, topical medications, interventional procedures, surgeries, and nontraditional treatments. Long-term therapies are often needed as the pain associated with the condition may last for years.


The initial treatment should be tailored to patient preferences, comorbidities, concomitant medication use, and desired medication side effect profiles. Common pharmacologic agents used for the treatment of PHN include anticonvulsants, antidepressants, topical agents, and opioids ( Table 20.1 ).

Table 20.1

A Summary of Pharmacologic Therapies for the Treatment of PHN.

Medication Mechanism of Action Initial and Titrating Dosage Adverse Effects
Gabapentin , , , , Inhibits voltage-gated calcium channels; prevents release of stimulatory neurotransmitters 100–300 mg at bedtime or in three divided doses; increase by 100 –300 mg every 5 days to a total daily dose of 1800 –3600 mg Somnolence, dizziness, ataxia, peripheral edema, xerostomia, weight gain
Pregabalin , , , , Inhibits voltage-gated calcium channels; prevents release of stimulatory neurotransmitters 50 mg three times per day or 75 mg twice daily; increase to maximum total daily dose of 600 mg Somnolence, dizziness, peripheral edema, xerostomia, weight gain
Tricyclic antidepressants
Amitriptyline , , , , Inhibits reuptake of norepinephrine and serotonin 10–25 mg at bedtime; increase by 10–25 mg weekly to target dose of 75 –150 mg per day Sedation, xerostomia, constipation, urinary retention, cardiac toxicity
Nortriptyline , , , , Inhibits reuptake of norepinephrine and serotonin 10–25 mg at bedtime; increase by 10–25 mg weekly to target dose of 75 –150 mg per day Sedation, xerostomia, constipation, urinary retention, cardiac toxicity
Morphine , , , Mu opioid receptor agonist 15 mg every 6 h as needed; dose escalation per provider’s discretion Nausea/vomiting, constipation, dizziness, drowsiness, potential for dependence and abuse
Oxycodone , , , Mu opioid receptor agonist 5 mg every 6 h as needed; dose escalation per provider’s discretion Nausea/vomiting, constipation, dizziness, drowsiness, potential for dependence and abuse
Tramadol , , , , Weak opioid agonist; serotonin and norepinephrine reuptake inhibitor 50 mg once or twice daily; dose escalation per provider’s discretion Nausea/vomiting, constipation, dizziness, drowsiness, increased risk of seizures
Topical therapies
Capsaicin , , , , Vanilloid type I receptor agonist 0.075% cream (up to 3–4 applications per day); 8% patch (application time of 30–90 min) Burning at the application site
Lidocaine , , , , Voltage-gated sodium channel blocker 5% patch; up to 3 patches per day for a maximum of 12 h Local erythema, pruritus

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Jan 3, 2021 | Posted by in PAIN MEDICINE | Comments Off on Postherpetic Neuralgia
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