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)