Major histocompatibility complex haplotype is associated with postherpetic pain in mice

Background: Postherpetic neuralgia is one of the major complications of herpes zoster caused by the reactivation of varicella-zoster virus and is characterized by severe pain. The authors previously showed the association of a human major histocompatibility complex (MHC) haplotype with postherpetic neuralgia. This study was performed to experimentally confirm the role of MHC haplotype in the development of postherpetic pain using a mouse model of postherpetic pain, which corresponds to postherpetic neuralgia. Methods: BALB/c mice (MHC haplotype: H-2(d)), C57BL/6 mice (MHC haplotype: H-2(b)), and BALB/b mice, a congenic BALB/c strain with H-2(b), were used. Herpes simplex virus type I was transdermally inoculated on the hind paw. Unilaterally zosteriform skin lesion and pain-related responses (acute herpetic pain) were caused, and some mice showed pain-related responses (postherpetic pain) after the cure of skin lesions. Herpes simplex virus type I antigen and CD3-positive cells were immunostained in the dorsal root ganglion in the acute phase. Results: The incidence (78%) of postherpetic pain in C57BL/6 mice was significantly higher than that (35%) in BALB/c mice (P = 0.004, odds ratio = 6.7). Furthermore, the incidence of postherpetic pain in BALB/b (H-2(b)) was similar to that in C57BL/6. Herpes simplex virus type I antigen-positive cells were less in the dorsal root ganglion of C57BL/6 mice than that of BALB/c mice. CD3-positive T cells were more in the dorsal root ganglion of C57BL/6 mice than BALB/c mice. Conclusions: These results suggest that the MHC haplotype (H-2(b)) is involved in the incidence of postherpetic pain, and CD3-positive T cells may play a role in its pathogenesis.