Although pain was previously not considered an important element of multiple 
sclerosis (MS), recent evidence indicates that over 50% of MS patients suffer 
from chronic pain. In the present study, we utilized the Theiler's murine 
encephalomyelitis virus (TMEV) model of MS to examine whether changes in 
nociception occur during disease progression and to investigate whether sex 
influences the development of nociception or disease-associated neurological 
symptoms. Using the rotarod assay, TMEV infected male mice displayed increased 
neurological deficits when compared to TMEV infected female mice, which mimics 
what is observed in human MS. While both male and female TMEV infected mice 
exhibited thermal hyperalgesia and mechanical allodynia, female mice developed 
mechanical allodynia at a faster rate and displayed significantly more 
mechanical allodynia than male mice. Since neuropathic symptoms have been 
described in MS patients, we quantified sensory nerve fibers in the epidermis of 
TMEV-infected and non-infected mice to determine if there were alterations in 
epidermal nerve density. There was a significantly higher density of PGP9.5 and 
CGRP-immunoreactive axons in the epidermis of TMEV-infected mice versus 
controls. Collectively these results indicate that the TMEV model is well suited 
to study the mechanisms of MS-induced nociception and suggest that alterations 
in peripheral nerve innervation may contribute to MS pain.