Contrasting genetic effects of major histocompatibility complex on ischemic peripheral nerve and spinal cord injury in female rats

We have recently shown that the major histocompatibility complex (MHC) exerts a regulatory influence on the development of neuropathic pain-like behaviors after partial sciatic nerve injury in male rats. In the present study, we assessed the role of the MHC in peripheral nerve injury-induced pain as well as central pain following spinal cord injury in female rats using the following inbred strains: Dark Agouti (DA; RT1^av1), Piebald Virol Glaxo (PVG; RT1^c) and in the MHC-congenic strain PVG–RT1^av1. In line with our previous observation in male rats, PVG–RT1^c displayed more severe allodynia compared to the strains carrying the RT1^av1 haplotype (PVG–RT1^av1 and DA–RT1^av1) following sciatic nerve injury in female rats. However, the MHC did not seem to impact the development of allodynia following spinal cord injury since the two congenic strains PVG–RT1^c and PVG–RT1^av did not differ after spinal cord injury. Interestingly, the DA–RT1^av1 strain displayed significantly more severe allodynia than both PVG strains and this difference was not explained by the extent of spinal cord injury. These results suggest that there are differences in the genetic mechanisms for neuropathic pain development following peripheral or central nervous system injury, both in regarding to the role of the MHC complex as well as non-MHC genes.