Postherpetic neuralgia: From preclinical models to the clinic

Neurotherapeutics, Oct 2009

Postherpetic neuralgia (PHN), a common complication of herpes zoster, which results from reactivation of varicella zoster virus, is a challenging neuropathic pain syndrome. The incidence and severity of herpes zoster and PHN increases with immune impairment or age and may become a greater burden both in terms of health economics and individual suffering. A clearer understanding of the underlying mechanisms of this disease and translation of preclinical outcomes to the clinic may lead to more efficacious treatment options. Here we give an overview of recent findings from preclinical models and clinical research on PHN.

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Postherpetic neuralgia: From preclinical models to the clinic

Ada Delaney 2 3 Lesley A. Colvin 0 2 Marie T. Fallon 1 2 Robert G. Dalziel 2 5 Rory Mitchell 2 4 Susan M. Fleetwood-Walker 2 3 0 Department of Anaesthesia , Critical Care, and Pain Medicine 1 Edinburgh Cancer Research Centre, Western General Hospital 2 wood-Walker, Ph.D., Centre for Neuroregeneration, Chancellor's Building , 49 Little France Crescent, University of Edinburgh , EH16 4SB, UK 3 Centre for Neuroregeneration 4 Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh , Edinburgh, United Kingdom 5 The Roslin Institute and Centre for Infectious Diseases Summary: Postherpetic neuralgia (PHN), a common complication of herpes zoster, which results from reactivation of varicella zoster virus, is a challenging neuropathic pain syndrome. The incidence and severity of herpes zoster and PHN increases with immune impairment or age and may become a greater burden both in terms of health economics and individual suffering. A clearer understanding of the underlying mechanisms of this disease and translation of preclinical outcomes to the clinic may lead to more efficacious treatment options. Here we give an overview of recent findings from preclinical models and clinical research on PHN. - Postherpetic neuralgia is a challenging chronic neuropathic pain syndrome. It occurs after reactivation of a latent infection by varicella zoster virus (VZV) within sensory neurons1 causes the distinctive clinical condition known as herpes zoster (HZ) and commonly called shingles. Although most patients recover completely after several months, a number will be left with persistent pain, known as postherpetic neuralgia (PHN). Currently available therapies are of variable benefit, and there is a clear need to improve our clinical approach either by improved treatments or by developing effective prevention strategies.1,2 The nature of the interaction between the virus and host cells is unclear and underinvestigated. The promise of eventual eradication by vaccination programs remains to be properly evaluated. The etiology of disease progression is poorly understood. After resolution of the primary infection, known as varicella or chickenpox, VZV establishes a latent infection in sensory ganglia that persists for the lifetime of the host.3 In some circumstances, often associated with increasing age or in situations of immune compromise, HZ may develop.4,5 Clinical features of HZ can be variable and include pain and abnormal sensations that may continue after the development of PHN.6 11 The incidence of HZ and PHN is difficult to estimate accurately because of inconsistencies in diagnosis and data collection. Studies indicate an incidence of 5.23 cases of HZ per 1000 person-years, with 13.7% of those having evidence of PHN after 3 months, or an incidence of 0.4 per 1000 person-years for PHN (compared with 0.15 for diabetic neuropathy).12,13 Estimates for HZ range from 5 to 12 cases per 1000 each year over all age groups.14 In the majority of patients presenting with HZ, the characteristic rash and associated acute zoster pain disappear within 12 months, but for some patients the acute symptoms of HZ may be followed by irreversible skin damage and sensory abnormalities, resulting in a persistent pain that can continue for months or years. Postherpetic neuralgia is the most common complication of HZ.15 Risk factors include age, severity of acute HZ pain, extent of rash, and presence and duration of prodromal pain.16 18 Other complications of HZ can include encephalitis, retinitis, and pruritus.19 The likelihood of developing PHN is unclear, because definitions vary between studies,20 and there is a need for an evidence-based description of the pain syndrome associated with PHN.21 Postherpetic neuralgia can manifest as a constant or intermittent spontaneous pain; in addition, sensory stimuli can evoke pain (e.g., dynamic mechanical allodynia evoked by innocuous stimulation, such as light touching of the skin).22,23 In addition, impaired sleep, emotional distress, and depression are common. In combination, these manifestations of PHN can lead to a reduction in the quality of life and activity levels. At present, zoster-associated pain is used to cover a continuum of pain from the start of prodrome to its resolution, with PHN reserved for cases of significant pain or painful abnormal sensations persisting beyond 3 months after the HZ rash. The time course for the development of persistent pain associated with PHN is between 90 and 120 days after rash appearance.24 27 The risk of PHN increases dramatically with age, from 3 4% in adults aged 30 49 years, to 21% in 60- to 69-yearolds, to 29% in 70- to 79-year-olds, and to 34% in adults over the age of 80 years.9,28 As the median age of the developed world population increases, PHN may become a greater burden. Approximately 70% of PHN patients who also experience ongoing pain and severe dynamic mechanical allodynia show considerable s (...truncated)


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Ada Delaney, Lesley A. Colvin, Marie T. Fallon, Robert G. Dalziel, Rory Mitchell, Susan M. Fleetwood-Walker. Postherpetic neuralgia: From preclinical models to the clinic, Neurotherapeutics, 2009, pp. 630-637, Volume 6, Issue 4, DOI: 10.1016/j.nurt.2009.07.005