EAE a pain in the face

Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease. 

We found that mechanical allodynia (increases sensitivitiy to movement/touch when it was not sensitive in the healthy animal) of the hind paw preceded the onset of clinical EAE but was unmeasurable at clinical peak (Not surprising as they can’t feel anything because the limb is anaesthetic because nerves aren’t signalling). This mechanical hypersensitivity coincided with increased microglial activation confined to the dorsal horn (The nerves that detect sensations enter the spinal cord through the dorsal horn.
The development of facial mechanical allodynia also emerged in preclinical EAE, persisted at the clinical peak, and corresponded with pathology of the peripheral trigeminal afferent pathway (The face also becomes sensitive to touch before signs of movement disease). This included T cell infiltration, which arose prior to overt central lesion formation and specific damage to myelinated neurons during the clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. 

These pain faces were seen after delivery of acute painful stimuli and now it is being said they are present in acute EAE. 

So more evidence for the Home Office to say this is a nasty, procedure that needs limiting.

Trust me in the UK they are doing this.

However, the problem with the acute EAE model is that it is not really a model of neuropathic pain as found in MS, because when they are detecting sensory problems the animals have not the experienced nerve damage that damage the neuropathic problems that are so difficult to treat.

We and the Home office have looked for the Grimace faces following the development of chronic disability and they are not there. Therefore, we think that these faces are only able to detect acute pain effects, which will respond to routine analgesics. 

We need something in addition to deal with the neuropathic pain condition in MS.

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    • Sorry. Animal research is distressing so is human disease.

      We could hide it behind pretty pictures that say Gu Gu GA GA but the government want us to educate and inform about these days issues so we don't want to hear de behind fluff.

      Luckily we were not presenting on epilepsy as they have seizures and that would be upsetting. If your son can see these faces in his animals he is doing something wrong.

      Our animals get the best of care and are protected by law since the 1890s.

    • He was distressed at the idea of mice getting the mouse equivalent of MS, when I explained this to him. He also questioned whether drugs that work for mice would work for people …

    • In our hands the drugs work even better because we can switch off disease within 24hours, but yes the drugs that work in MS generally work in mice the problem is there are more drugs that work in mice than people.

      Part of this failure is human error but we have reported on this previously

  • Indeed, it is difficult to model the pain associated with chronic disability in MS in the mouse. In the paper in question, facial grimacing was seen concurrent with motor disability (when "nerve damage" is clearly visible), but not before. This could be seen as a more translatable measure of pain than the evoked measures (allodynia) commonly used, which are only visible in sub clinical disease in the absence of significant neurodegeneration/inflammation.

    But I agree, the challenge is to find more translatable measures of pain in disease models in order to more effectively treat pain as it is experienced in humans with MS.

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