Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the primary symptoms of MS are losses of sensory and motor functions, it is now recognized that chronic pain is also a major concern affecting between 50% and 80% of MS patients. To date, however, few studies have examined the underlying mechanisms of chronic pain in MS or in the animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features of MS pathology. We, therefore, set out to characterize the changes in pain sensitivity that arises in a chronic-relapsing model of EAE. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG35–55) develop a robust allodynia to both cold and tactile stimuli. Allodynia emerges early in the disease process, often before any signs of neurological deficit and is independent of the overall symptom severity in these mice. “Classical” cellular substrates for neuropathic pain and allodynia such as altered expression of sensory neuropeptides in the dorsal horn of the spinal do not appear to underlie these changes in sensory function. There is, however, a significant influx of CD3+ T cells and increased astrocyte and microglia/macrophage reactivity in the superficial dorsal horn of mice with MOG35–55 EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG35–55 EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG35–55 EAE model is a useful tool to study neuropathic pain in MS.
aDept. of Anesthesiology and Pain Medicine, Clinical Sciences Building, 8-120, University of Alberta, Edmonton, Alta., Canada T6G-2G3
bCentre for Neuroscience, University of Alberta, Edmonton, Alta., Canada
*Corresponding author. Address: Dept. of Anesthesiology and Pain Medicine, Clinical Sciences Building, 8-120, University of Alberta, Edmonton, Alta., Canada T6G-2G3. Tel.: +1 780 492 3380; fax: +1 780 407 3200.
Submitted September 21, 2008; revised and accepted November 5, 2008.