Background     Postherpetic neuralgia (PHN) is a syndrome of zoster-associated pain persisting more than 3 months after resolution of an initial herpes zoster (HZ) rash (‘shingles’).

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 non-noxious 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 6 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).

Analgesic strategies     PHN is a quintessential neuropathic pain syndrome, and the analgesic approach is like other neuropathic syndromes. A systematic review found general analgesics (e.g., short course of opioids) and magnesium sulfate (often given IV at a dose of 30 mg/kg) as the most preferred analgesic agents; antiepileptics (e.g., gabapentin, pregabalin) and tricyclic antidepressants (TCAs) were considered secondary treatments, while antivirals appeared to be less favorable than these other classes (13).  Other guidelines cite strong evidence for TCAs, gabapentinoids (gabapentin, pregabalin), opioids, lidocaine 5% patch, and capsaicin 8% patch to manage PHN (14,15). (See Fast Facts #49, 148, 255, and 271). Strong evidence also supports combined therapy of gabapentin plus opioids or TCAs (15). Topical salicylate and topical capsaicin 0.075% cream (available over the counter) are less likely to offer meaningful pain reduction (16). Epidural steroid injections and acupuncture are likely no better than placebo (15). While serotonin norepinephrine reuptake inhibitors such as duloxetine are commonly used for neuropathic syndromes (see Fast Fact #187), there are no published trials specific to 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 (17).

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/12 hours ($217)
Capsaicin 8% patch	1 patch per 90 days ($265)	1 patch/ 90 days ($265)

References

1. Delaney A, Colvin LA, Fallon MT, et al. Postherpetic neuralgia: from preclinical models to the clinic.  Neurotherapeutics. 2009; 6:630–637.
2. Watson P. Postherpetic neuralgia. Clin Evid Handbook. June 2011;301-303.
3. Nagasako EM, Johnson RW, Griffin DR, Dworkin RH.  Rash severity in herpes zoster: correlates and relationship to postherpetic neuralgia.  J Am Acad Dermatol. 2002; 46(6):834.
4. Jung BF, Johnson RW, Griffin DR, Dworkin RH. Risk factors for postherpetic neuralgia in patients with herpes zoster.  Neurol. 2004; 62(9):1545-51.
5. Thyregod HG, et al.  Natural history of pain following herpes zoster. Pain. 2007; 128:148-156.
6. Johnson RW, Bouhassira D, et al. The impact of herpes zoster and post-herpetic neuralgia on quality of life.  BMC Med. 2010; 8:37.
7. Weinke T, Edte A, et al.  Impact of herpes zoster and post-herpetic neuralgia on patients’ quality of life: a patient-reported outcomes survey. Z Gesundh Wiss. 2010; 18(4):367-374.
8. Drolet M, Brisson M, Schmader KE, et al. The impact of herpes zoster and postherpetic neuralgia on health related quality of life: a prospective study.  CMAJ. 2010; 182(16):1731-6.
9. Center for Disease Control and Prevention (2013). Herpes Zoster Vaccination for Health Care Professionals. Retrieved from http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm. Accessed March 6, 2013.
10. Thakur R, Philip AG.  Treating herpes zoster and post herpetic neuralgia: an evidence based approach. J Fam Pract. 2012; 61(9 Suppl):S9-15.
11. Dworkin RH, Schmader KE. Epidemiology and natural history of herpes zoster and postherpetic neuralgia.  In Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia. 2nd ed. New York, NY: Elsevier Press; 2001:39-64.
12. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995; 123:89-96.
13. Song D, He A, et al.  Efficacy of pain relief in different postherpetic neuralgia therapies: a network meta-analysis. Pain Physician 2018; 21:19-32.
14. Attal N, Cruccu G, et al.  EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.  Eur J Neurol. 2010; 17:1113-1123.
15. Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H.  An evidence based report of the quality standards subcommitee of the American Academy of Neurology.  Neurol. 2004; 63:959-965.
16. Mou J, Paillard F, et al.  Efficacy of Qutenza ® (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database.  Pain 2013; 154(9): 1632-1639.
17. Drugstore.com Online Pharmacy. Available at http://www.drugstore.com. Accessed February 22, 2013.

Authors’ Affiliations:  National Institutes of Health Clinical Center, Bethesda, MD.
Conflicts of Interest Disclosure: The authors have not disclosed any relevant conflicts of interest.
Version History:  First published September 2013. Re-copy-edited by Sean Marks in September 2015; and again, in June 2021.