Infection by human varicella-zoster virus confers norepinephrine sensitivity to sensory neurons from rat dorsal root ganglia

Varicella-zoster virus (VZV) is a widespread human herpes virus causing chi cken pox on primary infection and persisting in sensory neurons. Reactivati on causes shingles, which are characterized by severe pain and often lead t o postherpetic neuralgia, To elucidate the mechanisms of VZV-associated hyp eralgesia, we elaborated an in vitro model for the VZV infection of sensory neurons from rat dorsal root ganglia. Between 35 and 50% of the neurons sh owed strong expression of the immediate-early virus antigens IE62 and IE63 and the late glycoprotein gE. When the intracellular calcium concentration was monitored microfluorometrically for individual cells after infection, t he sensitivity to GABA or capsaicin was similar in controls and in VZV-infe cted neurons. However, the baseline calcium concentration was increased. Ne urons became de novo sensitive to adrenergic stimulation after VZV infectio n, Norepinephrine-responsive neurons were more frequent and calcium respons es to norepinephrine were significantly higher after infection with wild-ty pe isolates than with the attenuated vaccine strain OKA. The adrenergic ago nists phenylephrine and isoproterenol had similar efficacy. We suggest that the infection with wild-type VZV isolates confers norepinephrine sensitivi ty to sensory neurons by using alpha (1)-and/or beta (1)-adrenergic recepto rs providing a model for the pathophysiology of the severe pain associated with the acute reactivation of VZV.