Study to Find Out if Therapy With the Drug Pregabalin Relieves Pain During Shingles Compared With Placebo

The varicella zoster virus (VZV) is the smallest of the double-stranded DNA herpes viruses,
and the only one capable of producing two different diseases, varicella (chickenpox) and
herpes zoster (acute herpes zoster [AHZ], shingles). The incidence of AHZ, and the
secondary VZV infection, is strongly age-dependent and reaches 1% per year by age 80 and
there are between 300,000 and 1 million new cases of AHZ each year in the US. AHZ is almost
always painful, and the pain can be of disabling severity, rendering some sufferers
bed-bound and too incapacitated to carry out normal activities, leading to weight loss and
dehydration sufficient to require inpatient therapy. The elderly are especially likely to
suffer severe pain.

The most common complication of AHZ is development of postherpetic neuralgia (PHN). Although
the overall incidence of PHN after AHZ is about 10%, the incidence has been reported to rise
as high as 80% in those over the age of 80. In all published studies, age and greater
severity of initial zoster pain are each found to significantly increase the risk of
developing PHN. Severe zoster pain is believed to correlate with a more severe cutaneous
outbreak, more severe inflammation of the nerve trunk, and possibly greater injury to
primary afferent nerve fibers.

There are two separate issues to address when discussing the pain of AHZ. The first is
managing the AHZ pain itself, because the burden of suffering is so high. The second is
reducing the incidence of PHN. Both issues need to be considered in trial design, in part
because severe AHZ pain is itself a risk factor for PHN. Studies of the analgesic effect of
pregabalin suggest an analgesic profile similar to that of gabapentin. We would therefore
predict, that pregabalin would reduce the pain associated with AHZ and possibly prevent
development of PHN.