Postherpetic NeuralgiaB02.8

After herpes zoster and often beyond the period of the actual skin changes, persistent, often unbearable, segmental pain with a typical, shooting character, also known as post-zosteric or post-herpetic neuralgia (PHN).

Post-zosteric neuralgia is a neuropathic pain syndrome that persists for more than 4 weeks and only occurs 3 months (>90 days) after the typical skin changes, after a pain-free interval. The post-zosteric neuralgia can significantly affect the quality of life of the affected person. About 10-30% of all >50 year olds develop this zoster complication. The pain is perceived differently as:

• constantly persistent
• recurrent
• lightning-like shooting in (as with light current contacts)
• allodynically occurring at the slightest touch.

Various research results indicate that reorganisation processes in the posterior horn and peripheral nerve damage due to demyelination of afferent sensory fibres and small-fibre degeneration are the causes of the development of PZN (Fields HL et al. 1998).

Occurring in 9-14% of all zoster patients and in 50% of patients with zoster over 60 years of age. In women and in patients with zoster ophthalmicus, post-zosteric neuralgia (PZN) appears to be more common. Deficiency of the immune system does not seem to be a risk for PZN.

Causal therapy of herpes zoster!

Mild to moderate pain:

• Paracetamol (e.g. Ben-u-ron Tbl./Supp.) 4-6 times/day 500-1000 mg p.o.

Severe pain, postzoster neuralgia:

• Carbamazepine (e.g., Tegretal Tbl.) initial 2 times/day 100-200 mg p.o., increase every 5 days by 200 mg, at dose > 800 mg/day, distribute to 4 ED; maintenance dose 800-1600 mg/day. Caveat. Check carbamazepine active levels in serum (normal value: 4-12 mg/l), BB, transaminases, creatinine every 5 days. In case of overdose extrapyramidal-motor disturbances.
• Alternative: Gabapentin (= anticonvulsant; e.g. ^Gabapentin® STADA) initially 1 time/day 300 mg, increase to 3 times/day 300 mg p.o.; further dose increase ,if necessary, with intact renal function (control of renal parameters!), by 300 mg/day each time up to a maximum dose of 3600 mg/day in 3 ED.
• Alternatively: Pregabalin (^Lyrica® ) initially 1 time/day 150mg, increase after 7 days to 300mg/day, after 7 more days increase to the maximum dose of 600mg/day. For patients of advanced age, start with 75mg/day and increase weekly by 75mg.
• Alternative: Valaciclovir in combination with gabapentin (Valciclovir 1 time/day 1000mg; gabapentin initial 300mg 1 time/day increase up to 3600mg/day. In a larger study of 133 pat. significant benefits were obtained over historical collectives with respect to pain (Lapolla et al. 2011).

Ischemia pain:

• Pain initially occurring on exertion, later possibly also at rest, as a result of inadequate blood flow with cramp-like pain on exertion; rapid improvement on unloading (e.g., standing still).

Burning pain at rest:

• Use of opioids such as tramadol (e.g., Tramal®) 2-3 times/day 100-300 mg p.o. or antidepressants such as amitriptyline (e.g., Saroten) in ascending doses of 10 mg/day (week 1), 25 mg/day (week 2), 50 mg/day (week 3), then continue according to effect and side effect.

Acute postzoster neuralgia or duration of illness > 3 months:

• Amitriptyline (e.g. Saroten) or nortriptyline (e.g. Nortrilen®) in ascending doses of 10 mg/day in the evening (week 1), 3 times/day 10 mg or 25 mg/day in the evening (week 2), 3 times/day 25 mg or 50 mg/day in the evening (week 3 u. 4), from week 5 dosing according to effect and side effect.
• Alternative: doxepin (e.g. Aponal®) 3 times/day 10-50 mg, imipramine (e.g. Tofranil®) 3 times/day 10-50 mg. The additional administration of 40-80 mg prednisolone (p.o. or i.v.) has beneficial effects on acute pain, but none on the development of chronic pain.

For neuralgiform pain:

• Carbamazepine (e.g., Tegretal®) in increasing doses, starting with 200 mg 1-2 times/day, increasing by 200 mg every 5 days. Above 800 mg distribution to 3-4 ED, maintenance dose 800-1600 mg/day, target serum level 5-10 g/l.
• Alternative: Baclofen (e.g. Lioresal®) 5-10 mg 3 times/day, increase by 5-10 mg every 3 days, maintenance dose 60 mg/day in 3-6 ED.
• If insufficient effect: Ibuprofen retard 3 times/day 800 mg. Alternative: Metamizole (e.g. Novalgin®) 4000 mg/day, acetylsalicylic acid 4000 mg/day, paracetamol 4000 mg/day. Ultima ratio: morphine test and appropriate setting.

Sympathetic blocks:

• Ganglion cervicale superius (involvement of 1st-2nd trigeminal branches): 0.03 mg buprenorphine on 2 ml 0.9% NaCl solution; 10 blocks every 2nd day.
• Stellate block (involvement of 3rd trigeminal branch-Th4): 5-10 ml of a local anesthetic such as 0.5% bupivacaine or 0.03 mg buprenorphine on 5 ml 0.9% NaCl solution; 10 blocks every 2nd day.
• Epidural catheter (involvement Th5-L5): 5-10 ml 0.25% bupivacaine, max 2 weeks.
• Alternatives: plexus catheter, paravertebral block, border cord block.

Adjunctive therapy: acupuncture, cryo-analgesia, pain management training, hypnosis.

Neural therapy: infiltration of the painful area with local anesthetic, e.g. lidocaine, leads to immediate disappearance of pain, lasting for hours; permanent effect after multiple repetitions.

Chinese phytotherapy: Huoluo xiaoling dan ("pill for patency of the reticular pathways") and/or Longdan xiegan tang ("Gentiana decoction"), each given for several weeks.

Accompanying:

0.025% - 0.05% capsaicin ointment (e.g. ^Dolenon®, ^Capsamol®). 5x daily for 4-6 weeks, thereafter as required. Initial pain intensification can be prevented by applying EMLA ointment or a benzocaine ointment.

5% lidocaine plaster (12h treatment break)

Average duration 6 months, at 5-10% up to 10 years. Cooperation with the anaesthetists.

With the adjuvanted inactivated vaccine Shingrix® , a therapeutic with high efficacy has been available since 2018 that offers long-lasting protection against zoster and zoster neuralgia. The compound has been used in a Phase III study program in 38,000 patients worldwide. Approval is for patients >50 years of age(EMA, although STIKO has not yet endorsed this recommendation and continues to recommend from >60 years of age). It should be used as early as possible in zoster infection. The intramuscular injections are applied 2x at intervals of 2 (possibly 6) months.

An additional high-dose administration of glucocorticoids shortens the phase of acute zoster pain. Steroidal therapy does not seem to have a positive effect on post-zoster neuralgia.

In a meta-analysis, pregabalin and gabapentin were compared (14 randomized controlled trials with 3,545 patients: 926 on pregabalin, 1,256 on gabapentin, and 1,363 on placebo). Both agents improved pain scores on the 11-item numeric rating scale. However, pregabalin reduced pain by a mean of 1.65 points more than gabapentin. Pregabalin also performed better on sleep disturbances. However, pregabalin significantly increased the risk of adverse effects such as weight gain, fatigue, and dizziness compared with placebo, whereas this was not evident with gabapentin (Cao X et al. 2022).

1. Arnold LM et al (2017) Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. Postgrad Med 129: 921-933.
2. Avijgan M et al.(2017) Postherpetic neuralgia: Practical Experiences Return to Traditional Chinese.
3. Medicine.J Acupunct Meridian Stud 10:157-164.
4. Cao X et al (2022): A Meta-analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Pregabalin and Gabapentin in the Treatment of Postherpetic Neuralgia. Pain Therapy DOI: 10.1007/s40122-022-00451-4.
5. Chen CJ et al (2003) Acupuncture, electrostimulation, and reflex therapy in dermatology. Dermatol Ther 16: 87-92
6. Dworkin RH et al (2003) Treatment and prevention of postherpetic neuralgia. Clin Infect Dis 36: 877-882
7. Fields HL et al (1998) Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 5:209-227.
8. Forbes HJ et al (2016) A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain 157:30-54.
9. Gilron I et al (2005) Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 352: 1324-1334.
10. Harden RN (2005) Chronic neuropathic pain. Mechanisms, diagnosis, and treatment. Neurologist 11: 111-122
11. Lapolla W et al (2011) Incidence of postherpetic neuralgia after combination treatment with gabapentin and valacyclovir in patients with acute herpes zoster: open-label study. Arch Dermatol 147:901-907.
12. Singh D et al (2003) The use of gabapentin for the treatment of postherpetic neuralgia. Clin Ther 25: 852-859
13. Weinberg JM et al (2003) Cutaneous infections in the elderly: diagnosis and management. Dermatol Ther 16: 195-205
14. Zenz M (1995) Pocketbook of pain therapy. Wissenschaftliche Verlagsgesellschaft mbH Stuttgart
15. Müller CSI et al (2021) Herpes zoster update-what's new? Akt Dermatol 47: 498-509
16. Hui F et al (2012) A randomized controlled trial of a multifaceted integrated complementary-alternative therapy for chronic herpes zoster-related pain. Altern Med Rev 17:57-68