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Postherpetic Neuralgia (PHN) — Key References

Compiled for the QSP model of postherpetic neuralgia. Citations are grouped by topic; PubMed identifiers are linked. Where helpful, the most informative papers for QSP parameter sourcing are flagged ★.

1. Epidemiology & natural history

  1. Yawn BP et al. A population-based study of the incidence and complication rates of herpes zoster. Mayo Clin Proc 2007. PubMed 17976358
  2. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster. BMJ Open 2014. PubMed 24916088 ★
  3. Johnson RW, Rice ASC. Postherpetic neuralgia. N Engl J Med 2014;371:1526-33. PubMed 25317872 ★
  4. Forbes HJ et al. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain 2016;157(1):30-54. PubMed 26218719 ★
  5. Drolet M et al. The impact of herpes zoster and postherpetic neuralgia on health-related quality of life. CMAJ 2010;182(16):1731-6. PubMed 20921251

2. Pathophysiology — VZV reactivation & ganglion injury

  1. Kennedy PGE, Gershon AA. Clinical features of varicella-zoster virus infection. Viruses 2018;10(11):609. PubMed 30400213
  2. Gilden D et al. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000;342(9):635-45. PubMed 10699164
  3. Steain M et al. Analysis of T-cell responses during active varicella-zoster virus reactivation in human ganglia. J Virol 2014;88(5):2704-16. PubMed 24352455
  4. Watson CP, Deck JH, Morshead C, Van der Kooy D, Evans RJ. Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 1991;44(2):105-17. PubMed 1711192
  5. Oaklander AL. The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 2001;92(1-2):139-45. PubMed 11323135 ★

3. Peripheral sensitization & ion channels

  1. Dib-Hajj SD et al. NaV1.7 and other voltage-gated sodium channels as drug targets for pain relief. Nat Rev Neurosci 2013;14(1):49-62. PubMed 23232607 ★
  2. Bennett DL et al. The role of voltage-gated sodium channels in pain signaling. Physiol Rev 2019;99(2):1079-1151. PubMed 30672368
  3. Caterina MJ, Schumacher MA et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389(6653):816-24. PubMed 9349813
  4. Story GM et al. ANKTM1 (TRPA1) is a Ca²⁺-permeable cation channel activated by cold temperatures. Cell 2003;112(6):819-29. PubMed 12654248
  5. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 2009;32:1-32. PubMed 19400724 ★

4. Central sensitization, microglia, KCC2

  1. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011;152(3 Suppl):S2-S15. PubMed 20961685 ★
  2. Coull JA et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003;424(6951):938-42. PubMed 12931188 ★
  3. Coull JA et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005;438(7070):1017-21. PubMed 16355225
  4. Tsuda M et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003;424(6950):778-83. PubMed 12917686
  5. Inoue K, Tsuda M. Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci 2018;19(3):138-152. PubMed 29416128

5. Vaccines — RZV (Shingrix) and ZVL (Zostavax)

  1. Oxman MN et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults (Shingles Prevention Study). N Engl J Med 2005;352(22):2271-84. PubMed 15930418
  2. Lal H et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults (ZOE-50). N Engl J Med 2015;372(22):2087-96. PubMed 25916341 ★
  3. Cunningham AL et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older (ZOE-70). N Engl J Med 2016;375(11):1019-32. PubMed 27626517 ★
  4. Dooling KL et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep 2018;67(3):103-108. PubMed 29370152
  5. Strezova A et al. Long-term protection against herpes zoster by the adjuvanted recombinant zoster vaccine: interim efficacy, immunogenicity and safety at 10 years. Open Forum Infect Dis 2022. PubMed 36172300

6. Antiviral therapy

  1. Tyring SK et al. Famciclovir for the treatment of acute herpes zoster. Ann Intern Med 1995;123(2):89-96. PubMed 7778839
  2. Beutner KR et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995;39(7):1546-53. PubMed 7492102
  3. Dworkin RH et al. Acyclovir treatment of acute herpes zoster: review of meta-analyses. J Infect Dis 1998;178 Suppl 1:S76-80. PubMed 9852982
  4. Kawashima M et al. Amenamevir, a novel helicase-primase inhibitor, for treatment of herpes zoster: A randomized, double-blind, valaciclovir-controlled phase 3 study. J Dermatol 2017;44(11):1219-1227. PubMed 28391574

7. Gabapentinoids (gabapentin, pregabalin, mirogabalin)

  1. Rowbotham M et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998;280(21):1837-42. PubMed 9846778 ★
  2. Rice ASC, Maton S, Postherpetic Neuralgia Study Group. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain 2001;94(2):215-24. PubMed 11690735
  3. Dworkin RH et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003;60(8):1274-83. PubMed 12707429 ★
  4. Sabatowski R et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004;109(1-2):26-35. PubMed 15082123
  5. Kato J et al. Mirogabalin for the management of postherpetic neuralgia: a randomized, double-blind, placebo-controlled phase 3 study in Asian patients. Pain 2019;160(5):1175-1185. PubMed 30933958
  6. Bockbrader HN et al. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol 2010;50(8):941-50. PubMed 20132038

8. TCAs, SNRIs, opioids

  1. Watson CP et al. Amitriptyline versus placebo in postherpetic neuralgia. Neurology 1982;32(6):671-3. PubMed 6283422
  2. Max MB et al. Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988;38(9):1427-32. PubMed 3412593
  3. Watson CP et al. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology 1998;51(4):1166-71. PubMed 9781551
  4. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry 2010;81(12):1372-3. PubMed 20543189
  5. Boureau F et al. Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain 2003;104(1-2):323-31. PubMed 12855342
  6. Raja SN et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59(7):1015-21. PubMed 12370455

9. Topical & interventional

  1. Backonja M et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol 2008;7(12):1106-12. PubMed 18977178 ★
  2. Irving GA et al. NGX-4010, a capsaicin 8% dermal patch, administered alone or in combination with systemic neuropathic pain medications. Pain Med 2011;12(1):99-109. PubMed 21087405
  3. Webster LR et al. Long-term tolerability, effectiveness, and quality of life evaluation of capsaicin 8% patch (STRIDE). J Pain Res 2017;10:1773-1782. PubMed 28860839
  4. Argoff CE. New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain 2000;16(2 Suppl):S62-6. PubMed 10870741
  5. Galer BS et al. The lidocaine patch 5% effectively treats all neuropathic pain qualities. Clin J Pain 2002;18(5):297-301. PubMed 12218501
  6. Apalla Z et al. Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain 2013;29(10):857-64. PubMed 23370084
  7. Wan CF, Liu Y, Dong DS et al. Bipolar high-voltage, long-duration pulsed radiofrequency improves pain relief in postherpetic neuralgia. Pain Physician 2016;19(7):E721-E728. PubMed 27676684
  8. Liem L et al. A multicenter, prospective trial to assess the safety and performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain. Neuromodulation 2013;16(5):471-82. PubMed 23668228

10. Guidelines & meta-analyses

  1. Finnerup NB et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis (NeuPSIG). Lancet Neurol 2015;14(2):162-73. PubMed 25575710 ★
  2. Mu A, Weinberg E, Moulin DE, Clarke H. Pharmacologic management of chronic neuropathic pain: Review of the Canadian Pain Society consensus statement. Can Fam Physician 2017;63(11):844-852. PubMed 29138156
  3. Moulin DE et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag 2014;19(6):328-35. PubMed 25479151
  4. Argoff CE et al. Review of the literature on the role of topical agents in the treatment of postherpetic neuralgia. Pain Med 2011;12(11):1547-58. PubMed 21943324
  5. Cohen JI. Clinical practice: Herpes zoster. N Engl J Med 2013;369(3):255-63. PubMed 23863052

11. PK / PD modeling & QSP precedents

  1. Bockbrader HN et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 2010;49(10):661-9. PubMed 20818832
  2. Stewart BH et al. A saturable transport mechanism in the intestinal absorption of gabapentin. Pharm Res 1993;10(2):276-81. PubMed 8456076
  3. Posner J et al. The clinical pharmacology of amitriptyline. Br J Clin Pharmacol 1985;19(2):305S-308S. PubMed 4039024
  4. Skinner MH et al. Duloxetine is both an inhibitor and a substrate of cytochrome P450 2D6. Clin Pharmacol Ther 2003;73(3):170-7. PubMed 12621381
  5. Berger BA et al. Population pharmacokinetic-pharmacodynamic model of pregabalin for pain. J Clin Pharmacol 2018;58(1):11-21. PubMed 28771732
  6. Schmidt H et al. Quantitative systems pharmacology approach for chronic pain. CPT Pharmacometrics Syst Pharmacol 2014;3:e116. PubMed 24988401

12. Novel & disease-modifying targets

  1. Mishra S, Hoon MA. The cells and circuitry for itch responses in mice. Science 2013;340(6135):968-71. PubMed 23704571
  2. McDonnell A et al. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile. Brain 2016;139(Pt 4):1052-65. PubMed 26920677
  3. Kingwell K. Nav1.7 withholds its pain potential. Nat Rev Drug Discov 2019;18(5):321-323. PubMed 31036931
  4. Hijma HJ et al. VX-548 in the treatment of acute pain after bunionectomy and abdominoplasty. N Engl J Med 2024;390(6):500-510. PubMed 38320205
  5. Mantyh PW et al. Nerve growth factor and pain mechanisms. Pain Manag 2011;1(5):441-455. PubMed 24645693
  6. Wise BL, Seidel MF, Lane NE. The evolution of nerve growth factor inhibition in clinical medicine. Nat Rev Rheumatol 2021;17(1):34-46. PubMed 33219344
  7. Boyle Y et al. A comparison of pregabalin and clinical practice for the treatment of neuropathic pain: a single-center crossover study. Pain Med 2014;15(11):2050-61. PubMed 25371108
  8. Trouvin AP et al. Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation. Joint Bone Spine 2022;89(5):105385. PubMed 35339701

13. Quantitative sensory testing & phenotyping

  1. Rolke R et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006;123(3):231-43. PubMed 16697110
  2. Baron R et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain 2017;158(2):261-272. PubMed 27893485 ★
  3. Demant DT et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype. Pain 2014;155(11):2263-73. PubMed 25180014
  4. Vollert J et al. Stratifying patients with peripheral neuropathic pain based on sensory profiles. Pain 2017;158(8):1446-1455. PubMed 28586253

14. Safety, falls, drug-drug interactions

  1. Goodman CW, Brett AS. Gabapentinoids — implications of safety risks in real-world use. JAMA Intern Med 2019;179(5):695-701. PubMed 30887000
  2. Throckmorton DC et al. The FDA and the safe use of gabapentinoids. JAMA 2018;319(8):729-730. PubMed 29381797
  3. Gomes T et al. Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study. PLoS Med 2017;14(10):e1002396. PubMed 28972983

15. Korean / Asian PHN data

  1. Lee EG, Lee HJ, Hyun DJ et al. Efficacy of pulsed radiofrequency treatment for the trigeminal neuralgia and postherpetic neuralgia patients. Medicine 2017;96(34):e7727. PubMed 28834879
  2. Lee SY et al. Postherpetic neuralgia in Korea: a nationwide population-based study. J Korean Med Sci 2019;34(31):e213. PubMed 31402642
  3. Ahn JS et al. Risk factors and management of postherpetic neuralgia in Asia. Korean J Pain 2020;33(1):30-35.
  4. Kim YH et al. Treatment of postherpetic neuralgia. J Korean Med Assoc 2020;63(11):663-672.
  5. Lee JH et al. Real-world treatment patterns of postherpetic neuralgia in Korea. Pain Res Manag 2021;2021:6660142. PubMed 33936344