Animal Models and Pharmacology of Herpetic and Postherpetic Pain

Abstract

Varicella-zoster virus (VZV) causes varicella upon primary infection and subsequently becomes latent in the sensory ganglia. Reactivation of latent VZV in the sensory ganglion results in herpes zoster, which usually begins with pain and dysesthesia. Pain that persists long after healing of the rash is termed postherpetic neuralgia. VZV inoculation into rats induces mechanical allodynia and thermal hyperalgesia without causing herpes zoster. As with VZV, herpes simplex virus 1 (HSV1) is an alphaherpesvirus. HSV1 also becomes latent in the sensory ganglia after primary infection, and reactivation of latent HSV1 in the sensory ganglion results in herpes simplex. HSV1 inoculation into mice causes zoster-like skin lesions together with mechanical allodynia and mechanical hyperalgesia. A marked difference between the two rodent models is whether the herpes virus proliferates in the nervous system after inoculation. VZV-inoculated rats are useful for investigating mechanical allodynia induced by latent infection with herpes virus. HSV1-inoculated mice are useful for investigating mechanical allodynia induced by the proliferation of herpes virus in sensory neurons and for assessing the effects of acute herpetic pain on the incidence of postherpetic allodynia.

Corydalis decumbens Can Exert Analgesic Effects in a Mouse Neuropathic Pain Model by Modulating MAPK Signaling

“…Patients with PHN often exhibit profound mechanical allodynia and impairment of thermal sensitivity [9,10]. While mechanical allodynia and hyperalgesia can be induced by an inoculation with varicella zoster virus or herpes simplex virus type 1 on the hind paw of rats or mice, the viral infection models are often incapable of inducing thermal impairment and have the shortcoming of developing tissue inflammation, skin lesions, and paralysis through spreading of the virus in the central nervous system [11][12][13]. Previous studies have demonstrated that systemic treatment with resiniferatoxin (RTX), an ultrapotent transient receptor potential vanilloid 1 (TRPV1) agonist, generates long-lasting paradoxical changes in thermal and mechanical sensitivities and can replicate the unique clinical symptoms of patients with PHN [14,15].…”

Rodent models of postherpetic neuralgia: How far have we reached?

“…However, the mechanical allodynia and mechanical hyperalgesia generally last for 21 days ( 34 , 36 ). In this model, the thermal hyperalgesia are not observed during the outbreak and presence of herpes, but was induced in the post-herpes phase ( 49 ).…”

“…Different from the other neuropathic pain, VZV establishes a latent infection in the host. No evidence proved that VZV could proliferate in the nervous system ( 49 ), but viral DNA and transcripts have been detected in the DRG of the rodents after infection ( 34 , 51 ). Some reports suspect that transcription of VZV genes within virus-infected neurons may lead to the chronic pain, either through induction of inflammatory mechanisms or through expression of proteins, such as transcriptional regulators that alter host cell expression patterns.…”