Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE)

Pain. 2009 Jan;141(1-2):156-64. doi: 10.1016/j.pain.2008.11.002. Epub 2008 Dec 11.

Abstract

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 (MOG(35-55)) 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 MOG(35-55) EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG(35-55) EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG(35-55) EAE model is a useful tool to study neuropathic pain in MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / complications*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Gliosis / pathology
  • Glycoproteins
  • Hyperalgesia / etiology
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / physiology
  • Myelin-Oligodendrocyte Glycoprotein
  • Neuralgia / etiology*
  • Neuralgia / metabolism
  • Pain Threshold / physiology*
  • Peptide Fragments
  • Reaction Time
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • monocyte-macrophage differentiation antigen
  • myelin oligodendrocyte glycoprotein (35-55)
  • Calcitonin Gene-Related Peptide