Pain, nerve trunk inflammation, and neuronal injury are hallmarks of acute herpes zoster (AHZ or 'shingles'). The majority of patients with AHZ recover uneventfully, but a minority develop enduring neuropathic pain - in the form of post-herpetic neuralgia (PHN). Age, initial pain severity, and psychosocial factors have been established as risk factors for PHN in longitudinal studies, but evolution of neural dysfunction and deafferentation, the hallmarks of the chronic neuropathic pain of PHN, have received little study. We hypothesize that the development of post-herpetic neuralgia strongly depends on two factors: 1) the severity of the initial neural injury and 2) the ability to recover from the initial neural injury. To test this hypothesis, we will prospectively follow 200 patients with AHZ at high risk for development of PHN. Study participants will be followed closely from 2 weeks after the onset of AHZ to 6 months post-zoster, a time when PHN is well established and unlikely to remit spontaneously. Evolution of pain and neural injury will be evaluated at 2 weeks, 1 month, 3 months, and 6 months after the onset of AHZ. At study visits, assessments will include ratings of pain intensity, mood, quality of life, allodynia severity, mapping the extent of skin affected by lesions, pain, and allodynia, quantitative tests of sensory function, and response to controlled applications of capsaicin. Loss and possible recovery of cutaneous nerve fibers will be documented through serial skin punch biopsies stained for the axonal marker PGP 9.5 in affected and normal skin. Abnormal neural function in remaining fibers will be evident as allodynia, hyperalgesia to mechanical and thermal stimuli, and hyperalgesia to capsaicin application. Signs of loss of primary afferent nociceptor function will be evident as inability to perceive noxious heat and capsaicin. The importance of neural dysfunction and neuronal loss as risk factors for PHN will be compared to risk factors found in other studies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-4 (01))
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Porter, Linda L
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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