Post herpetic Neuralgia
Refers to pain following an infection with Varicella Zoster Virus (VZV). No consensus has been reached on its definition but a reliable description is a pain that persists for varying time duration after a healed Herpes Zoster (HZ) rash. The interval may be from 4 weeks to 6 months. The pain distribution is dermatomal and described as a persistent sharp, burning, aching or shooting sensation in the area of the rash. Frequently there is hyperalgesia and allodynia.
Pre disposing factors
- Age
- Sex
- Severity of pain at presentation with Herpes Zoster infection
- Presence and duration of pain, dysesthesia and allodynia in the prodrome to the rash
- Increased levels of VZV DNA
- Surgical interventions and mechanical trauma
- Smoking
- Depression and severity of HZ
Pathophysiology
Though not fully understood the mechanisms involved in PHN are believed to be due to a multifactorial influence of peripheral and central sensitization, deafferentiation, Glial cell activation and persistent neuronal inflammation.
Prevention of PHN
Post herpetic neuralgia only follows infection with VZV. Focus on prevention aims to protect against, reduce the severity and duration of the infection. Vaccination with a wild type VZV Oka strain was associated with a decreased incidence of PHN in 66.5% of the old patients enrolled. 1 Antiviral treatment (acyclovir, famclovir, valacyclovir) started within 72 hours after eruption of HZ vesicles has been shown to accelerate the healing process and possibly decrease the pain burden of PHN.2,3,4 Doubts however, have been cast on whether treatment with antiretroviral can reduce or prevent PHN.5,6
Despite this, investigators continue to explore treatment options in preventive medicine. A combination of an antiviral Valacyclovir and gabapentin showed a reduced incidence of PHN at since months.7
Treatment
As a result of the knowledge gap in fully understanding the exact pathophysiology of PHN, specific treatment is lacking. It is hence common practice to use a multidisciplinary approach to managing its debilitating effects. This section however, only addresses pharmacological and interventions as options.
Tricyclic antidepressants
Thought to reduce pain by blocking the re-uptake of serotonin and norepinephrine. Common side effects: sedation , orthostatic hypotension, constipation, cognitive decline. QT prolongation in elderly and cardiac patients is of concern.
Drugs: amitriptyline, nortriptyline and desipriamine. 8
Anticonvulsants
Reduce pain by acting as a membrane stabilizer, binding to the α2β subunit of the L-type calcium channel
Common side effects: drowsiness, dizziness, ataxia, mild peripheral edema, worsening of cognitive impairment in the elderly.
Drugs: Gabapentin and pregabalin.9,10 Oxycarbazepine.11
Opioids
Exert analgesic effects by acting on opioid receptors involved in pain modulation.
Tramadol is a weak opioid with a dual mechanism. It acts by activating μ-opioid receptors and decreasing reuptake of norepinephrine and serotonin.
Common side effects: sedation, constipation , pruritis, nausea, vomiting, orthostatic hypotension. Tramadol is unique as it increases the risk of serotonin syndrome in patients taking TCAs, Selective serotonin reuptake inhibitors and mono amine oxidase inhibitors.
Drugs: Oxycodone, Morphine12,13,14, tramadol15
Topical Local Anesthetics
5% Lidocaine patch 16,17
Inhibits neuronal sodium channels
Common side effects: skin irritation at application site
0.075%, 8% Capsaicin (cream/patch) 18
Initially excites nociceptive afferents then desensitizes unmyelinated epidermal nerve fibers.
Common side effects: local irritation, burning sensation
Interventions
Though it seems the benefit of treating PHN with interventions is justified, there is inadequate evidence to support its use. Efficacious studies that would be considered cost effective and with minimal side effects are limited to interlaminar injections with or without steroid19,20,21, paravertebral injections22 and selective sympathetic nerve blocks.23,24
REFERENCES
1.Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent her- pes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–2284.
- Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta-analysis. Arch Intern Med. 1997;157:909–912.
- Wood MJ, Kay R, Dworkin RH, Soong SJ, Whitley RJ. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebocontrolled trials. Clin Infect Dis. 1996;22:341–347.
- Dworkin RH, Boon RJ, Griffin DR, Phung D. Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients. J Infect Dis. 1998;178 Suppl 1:S76–S80.
- Lancaster T, Silagy C, Gray S. Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials. Br J Gen Pract. 1995;45:39–45.
- Alper BS, Lewis PR. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia? J Fam Pract. 2000;49:255–264.
- Lapolla W, Digiorgio C, Haitz K, et al. Incidence of postherpetic neu-ralgia after combination treatment with gabapentin and valacyclovir in patients with acute herpes zoster: open-label study. Arch Dermatol. 2011;147(8):901–907.
- Hempenstall K, Nurmikko TJ, Johnson RW, A’Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2:e164.
- Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998;280:1837–1842.
- Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs. 2005;65:111–118, discussion 119–120.
- Criscuolo S, Auletta C, Lippi S, Brogi F, Brogi A. Oxcarbazepine monotherapy in postherpetic neuralgia unresponsive to carbamazepine and gabapentin. Acta Neurol Scand. 2005;111:229–232.
- Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology. 1998;50:1837–1841.
- Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain. 2003;105:71–78.
- Raja SN, Haythornthwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2002;59:1015–1021.
- Hempenstall K, Nurmikko TJ, Johnson RW, A’Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2(7):e164.
- Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;2:CD004846.
- Watson CP, Tyler KL, Bickers DR, Millikan LE, Smith S, Coleman E. A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther. 1993;15:510–526.
- Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study.Lancet Neurol. 2008;7:1106–1112.
- Pasqualucci A, Pasqualucci V, Galla F, et al. Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand. 2000;44:910–918.
- van Wijck A, Opstelten W, Van Essen GA. Herpes zoster en post-herpetische neualgie: beleid in eerste en tweede lijn. NTTP. 2003;22:18–21.
- van Wijck AJ, Opstelten W, Moons KG, et al. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial.Lancet. 2006;367:219–224.
- Maroof, M. et al. Repetitive paravertebral nerve block using a mixture of ketamine, bupivacaine and methylprednisolone for pain relief in intractable post herpetic neuralgia. The Journal of Pain, Volume 9, Issue 4, 33
- Janig W, Levine JD, Michaelis M. Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. Prog Brain Res. 1996;113:161–184.
- Wu CL, Marsh A, Dworkin RH. The role of sympathetic nerve blocks in herpes zoster and postherpetic neuralgia. Pain. 2000;87: 121–129.