Postherpetic Neuralgia #272

Background

Postherpetic neuralgia (PHN) is a syndrome described as zoster-associated pain persisting for more than three months after resolution of an initial herpes zoster (HZ) rash (‘shingles’). This Fast Fact discusses PHN.

Epidemiology

Inconsistencies in diagnosis and data collection make the incidence of HZ and PHN difficult to estimate.^1,2 PHN develops rarely in those under 50 years. However, it occurs in 20% of persons 60 to 65 with HZ, and its incidence rises to 30% in persons over 80 years old.^1,2 Risk factors for PHN include severe acute shingles-related pain, rash severity (i.e., more than 50 lesions), increasing age, and immunocompromised status.^3,4

Pathophysiology

In acute HZ, reactivation of the virus from the dorsal root ganglia of spinal or cranial nerves causes inflammation and damage to the affected nerve tissue, resulting in acute pain. Subsequently, primary afferent neurons responding to the acute neuronal damage of zoster reactivation can cause sensitization of the nociceptive dorsal horn neurons, resulting in a prolonged exaggerated response to nonnoxious stimuli.¹ This central sensitization is thought to be a key mechanism in the development and maintenance of the pain of PHN.

Natural History

Most HZ patients experience resolution of the rash and acute HZ pain within two months.¹ For those who develop PHN, prolonged severe disabling symptoms rarely remain beyond six months.⁵ A small subset may experience irreversible damage to skin and sensory abnormalities that can result in ongoing pain for years.² For all patients with acute HZ and/or PHN, physical and emotional quality of life can be affected.^6–8

Prevention

In adults over 60 years old, live vaccination against the zoster virus reduces overall incidence of HZ by 50% and PHN by two-thirds. It is contraindicated in patients with immune deficiencies (primary or acquired, such as patients with leukemia), including patients taking immunosuppressants or high dose corticosteroids.⁹ Initiating antiviral drugs within 72 hours of rash onset reduces acute and chronic pain associated with HZ. There is no clear benefit to initiation after this window.^10–12 Best available evidence does not support the routine use of glucocorticoids in preventing PHN.¹⁰

Pain Management Strategies

PHN is a quintessential neuropathic pain syndrome and the approach to treatment is similar to other neuropathic syndromes. Recent guidelines cite strong evidence for using tricyclic antidepressants (TCAs), gabapentinoids (gabapentin, pregabalin), opioids, lidocaine 5% patch, and capsaicin 8% patch to manage PHN.^13,14 (See Fast Facts #49, 148, 255, and 271 for more information about these drugs.) Strong evidence also supports combined therapy of gabapentin plus opioids or TCAs.¹⁴ Second-line therapies include topical salicylate and topical capsaicin 0.075% cream. To date, evidence demonstrates that epidural steroid injections and acupuncture are no better than placebo.¹⁴ While serotonin norepinephrine reuptake inhibitors such as duloxetine are commonly used for neuropathic syndromes (see Fast Fact #187), there are currently no published trials regarding their use for PHN.

Cost

There is limited literature regarding cost effectiveness among commonly used agents. The following table provides current information regarding starting dose, effective dose, and cost.¹⁵

Drug	Starting dose (cost in USD/month)	Typical effective dose (cost/month)
Gabapentin 300 mg capsule	900 mg/day ($19)	1800 mg/day ($99)
Pregabalin 50 mg capsule	150 mg/day ($180)	450 mg/day ($180)
Desipramine 25 mg tablet	25 mg/day ($38)	100 mg/day ($99)
Nortriptyline 50 mg capsule	50 mg/day ($20)	75 mg/day ($20)
Lidocaine 5% patch	1 patch per 12 hours ($217)	1 patch per 12 hours ($217)
Capsaicin 8% patch	1 patch per 90 days ($265)	1 patch per 90 days ($265)