What causes postherpetic neuralgia (PHN) after herpes zoster (shingles) and why do some individuals develop it while others do not?

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What Causes Postherpetic Neuralgia After Shingles

Postherpetic neuralgia develops when the varicella zoster virus reactivates from dormancy in the dorsal root ganglia, travels along nerve pathways causing inflammation and direct nerve damage, which leads to persistent neuropathic pain that can last months to years after the rash resolves. 1

Pathophysiology of Nerve Damage

The mechanism involves several key steps:

  • Viral reactivation and nerve inflammation: The varicella zoster virus remains dormant in sensory ganglia after primary chickenpox infection, and upon reactivation, it causes direct inflammatory damage to peripheral nerves as it travels along dermatomal distributions 1

  • Nerve fiber destruction: The acute infection causes inflammatory necrosis of dorsal root ganglia, often with associated neuritis, leptomeningitis, and segmental degeneration of motor and sensory nerve roots 2

  • Persistent neuropathic changes: This nerve damage results in both peripheral nerve fiber dysfunction and central brain changes that perpetuate the pain signal even after the rash has healed 3, 1

Why Some People Develop PHN and Others Don't

The most critical determinant is age, with a clear dose-response relationship:

  • Age is the dominant risk factor: At least 50% of shingles patients over age 65 develop PHN (defined as pain persisting ≥3 months after rash onset), while 40% of those over 50 and 75% of those over 75 develop it 4, 5

  • Severity of acute pain: Greater pain intensity during the acute shingles episode strongly predicts PHN development 5, 6

  • Extent of rash: More widespread rash, particularly extending beyond a single dermatome, increases PHN risk 5

  • Prodromal pain: Presence of pain before the rash appears is associated with higher PHN rates 5

  • Viremia: Detection of viral DNA in blood at presentation is significantly associated with pain persistence at 6 months or beyond 6

  • Trigeminal distribution: Facial involvement carries somewhat higher risk, though this is less important than age and pain severity 4

Clinical Impact

PHN is definitively the most common complication of herpes zoster, affecting 15.9% of all patients at 6 months and 9% at one year in community studies 7, 6. The pain is typically described as burning, tingling, itchy, or stabbing, with both constant and paroxysmal components, often accompanied by allodynia (pain from light touch) 3, 5.

Prevention Strategy

The most effective approach to preventing PHN is vaccination against herpes zoster, with two available vaccines: zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV), particularly important for older adults who face the highest risk 1, 7.

For acute shingles, early treatment with systemic antivirals (acyclovir, valacyclovir, or famciclovir) within 72 hours of rash onset may reduce PHN incidence, and pre-emptive treatment with low-dose tricyclic antidepressants (amitriptyline or nortriptyline 10-25 mg at bedtime) from the time of acute shingles diagnosis reduces PHN incidence by approximately 50% 4, 2.

Common Pitfall

In community practice, only 50% of high-risk elderly patients receive appropriate antiviral therapy, mainly due to presentation beyond 72 hours after rash onset, representing a missed opportunity for prevention 6.

References

Guideline

Shingles and Neuropathic Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Postherpetic neuralgia: the never-ending challenge.

Pain practice : the official journal of World Institute of Pain, 2005

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The management of postherpetic neuralgia.

Postgraduate medical journal, 1997

Guideline

Postherpetic Neuralgia Complications and Prevention

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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