Acute and
chronic pain (post-herpetic
neuralgia or PHN) are encountered in patients with
herpes zoster that is caused by reactivation of varicella-zoster virus (VZV) from a state of neuronal latency. PHN is often refractory to current treatments, and additional strategies for
pain relief are needed. Here we exploited a rat footpad model of PHN to show that herpes simplex virus (HSV) vector-mediated gene delivery of human
preproenkephalin (vHPPE) effectively reduced chronic VZV-induced nocifensive indicators of
pain. VZV inoculated at the footpad induced prolonged
mechanical allodynia and
thermal hyperalgesia that did not develop in controls or with ultraviolet light-inactivated VZV. Subsequent footpad administration of vHPPE relieved VZV-induced
pain behaviors in a dose-dependent manner for extended periods, and prophylactic vector administration prevented VZV-induced
pain from developing. Short-term
pain relief following low-dose vHPPE administration could be effectively prolonged by vector re-administration. HPPE transcripts were increased three- to fivefold in ipsilateral ganglia, but not in the contralateral dorsal root ganglia. VZV
hypersensitivity and its relief by vHPPE were not affected by peripheral delivery of
opioid receptor agonist or antagonist, suggesting that the efficacy was mediated at the
ganglion and/or spinal cord level. These results support further development of ganglionic expression of
enkephalin as a novel treatment for the
pain associated with
Zoster.