Association of denervation severity in the dermis with the development of mechanical allodynia and hyperalgesia in a murine model of postherpetic neuralgia.

ABSTRACT

BACKGROUND: Postherpetic neuralgia (PHN) is a common complication of herpes zoster and remains a challenging condition of neuropathic pain. Allodynia, a prominent feature of PHN, extends beyond the margins of the initial rash area. In the present study, we investigated the association between cutaneous denervation and the development of postherpetic allodynia and hyperalgesia by using a murine model of PHN. METHODS: Female C57BL/6j mice were used. Herpes simplex virus type-1 (HSV1) was inoculated on the unilateral shin, a region that is predominantly innervated by L3 dorsal root ganglion (DRG) neurons. After the zoster-like skin lesions healed, mice were classified by the presence of mechanical allodynia and hyperalgesia in the plantar aspect of the ipsilateral hindpaw. Scarred lumbar (innervated by L2-4 DRG neurons) and the ipsilateral plantar (innervated by L3-5 DRG neurons) skin sections were immunostained with an antibody against protein gene product (PGP)9.5. The number of PGP9.5-immunoreactive (IR) profiles in the epidermis and dermis were analyzed for quantification of cutaneous innervation. RESULTS: In the epidermis of the scarred lumbar skin, the intraindividual mean number of PGP9.5-IR profiles was significantly decreased in mice inoculated with HSV1. The intraindividual maximum and mean numbers of PGP9.5-IR profiles in the epidermis of the scarred skin were not significantly different between mice with and without postherpetic allodynia and hyperalgesia. In the dermis of the scarred lumbar skin, the intraindividual maximum and mean numbers of PGP9.5-IR profiles were significantly decreased in mice with postherpetic allodynia and hyperalgesia, but not in mice without these symptoms. The intraindividual minimum number of PGP9.5-IR profiles in the dermis and epidermis was significantly decreased by HSV1 inoculation. HSV1 inoculation significantly decreased the intraindividual mean number of PGP9.5-IR profiles in the epidermis, but not dermis, of the plantar skin on the inoculated side. CONCLUSIONS: The present results suggest that the severity of dermal denervation in the scarred skin is associated with the development of postherpetic allodynia and hyperalgesia that extend beyond the margins of the initial rash area. The decrease of epidermal nerve density in the scarred and stimulation skins may not be associated with postherpetic allodynia and hyperalgesia.