A model of virus-induced hyperalgesia in rats

Abstract

ABSTRACT The link between infection and hyperalgesia has been determined using mainly lipopolysaccharide, which is a bacterial antigen. The relationship between viral infection and hyperalgesia has yet to be fully characterized, with current models of virus-induced hyperalgesia being based on infections by specific neurotrophic viruses. Therefore, the aim of this series of studies was to develop a general model of virus-induced hyperalgesia by injecting a pyrogenic and non-pyrogenic dose of Poly I:C, a synthetic, double-stranded ribonucleotide that is similar to the double-stranded ribonucleotides produced by almost all viruses, into rats’ tails. To identify a pyrogenic and non-pyrogenic dose of Poly I:C, male Sprague Dawley rats were injected subcutaneously in the tail either with saline (n=8) or 100 μg.kg-1 (n=8) or 1000 μg.kg-1 (n=8) Poly I:C. Only rats that received 1000 μg.kg-1 Poly I:C developed fever. Subsequently, in a separate experiment, tail withdrawal latencies to noxious thermal (49° water) and mechanical stimuli (4N blunt force) were recorded for six days after subcutaneous injection of 100 μg.kg-1 or 1000 μg.kg-1 Poly I:C or saline in male Sprague Dawley rats. I also took skin tissue samples from the site of injection to determine the histological changes that occur after Poly I:C injection. Thermal hyperalgesia was not elicited by Poly I:C injection. However, biphasic mechanical hyperalgesia developed in the animals receiving 100 μg.kg-1 Poly I:C, and sustained mechanical hyperalgesia, that lasted for four days, was evident in animals injected with 1000 μg.kg-1 Poly I:C. Mild sustained inflammation, at the injection site of both doses of Poly I:C, was present even after the hyperalgesia had subsided. This study provides evidence for a novel model of virus-induced hyperalgesia that is applicable to most cutaneous viral infections. More importantly, this model can be used to further our understanding of the mechanisms that underlie virus-induced pain.