weakness, tremor, or paralysis if the nerves involved also control muscle movement. Pathophysiology Postherpetic neuralgia is thought to be due to nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain, and may persist or recur for months, years, or for life. A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia neurons. Injury to sensory nerves induces neurochemical, physiological, and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory interneuron loss. Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and TRPV1 channels. These changes contribute to increased NMDA glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia. Diagnosis Lab Studies: No laboratory work is usually necessary. Results of cerebrospinal fluid evaluation are abnormal in 61%. Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%. These findings are not predictive of the clinical course of postherpetic neuralgia. Viral culture or immunofluorescence staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically. Antibodies to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out. Imaging studies: Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients. At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia. Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain. Epidemiology In the United States each year approximately 1,000,000 individuals develop herpes zoster, with nearly 1 in 3 people in the United States developing it in their lifetime. Of those individuals, approximately 10–18% develop postherpetic neuralgia. The incidence of herpes zoster, and also developing postherpetic neuralgia, both increase with age. The frequency and severity of