Microglia Key to Neuropathic Pain

While much is written about gimped NMDA receptors in chronic pain, the innocuous support tissues in the spinal cord, the “glial cells”, turn out to be a big player. An inhibitor of these cells, clopidogrel – known as Plavix – (an anti-platelet drug used in some instead of aspirin to prevent stroke) – surprisingly works to prevent this in animal studies

J Neurosci. 2008 May 7;28(19):4949-56.
P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K.

abstract here

  • “Emerging evidence has indicated that activated spinal microglia responding to nerve injury are key cellular intermediaries in the resulting highly debilitating chronic pain state, namely neuropathic pain.”
  • “the level of P2Y(12)R mRNA expression was markedly increased in the spinal cord ipsilateral to the nerve injury”
  • “Blocking spinal P2Y(12)R by the intrathecal administration of its antagonist AR-C69931MX prevented the development of tactile allodynia (pain hypersensitivity to innocuous stimuli), a hallmark of neuropathic pain syndrome.”
  • “mice lacking P2ry(12) (P2ry(12)(-/-)) displayed impaired tactile allodynia after nerve injury without any change in basal mechanical sensitivity.”
  • “a single intrathecal administration of AR-C69931MX or oral administration of clopidogrel (a P2Y(12)R blocker clinically in use) to nerve-injured rats produced a striking alleviation of existing tactile allodynia.”
  • “Together, our findings indicate that activation of P2Y(12)Rs in spinal microglia may be a critical event in the pathogenesis of neuropathic pain and suggest that blocking microglial P2Y(12)R might be a viable therapeutic strategy for treating neuropathic pain.”

Comment – The real culprits in neuropathic pain may be the glial cells – the support tissues in the spinal cord and brain. Future treatments are going to entail treatments directed against them. A search of clopidogrel found nothing in use for neuropathic pain. A glial cell inhibitor, minocycline or doxycycline forms of tetracycline, have shown to have minor effects on chronic pain in diseases like Rheumatoid arthritis. More work needs to be done.

Would be interested in thoughts on this subject.

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2 Responses to Microglia Key to Neuropathic Pain

  1. Pingback: Pain Medical Musing » Blog Archive » Attenuation of Pain After Spinal Injury May be Possible

  2. John Marr says:

    Recent studies indicate that defective and/or overactivated microglia may play a role in Apserger’s syndrome symptomization and other studies indicate a similar association with schizophrenia. This possible effect is termed in part an “immune system disorder.” It might be possible that migraine pain associated with peripheral nerve damage ascribed to microglia arises from overactivation of the glial cells and/or from defective micgroglia. In either case, it might be effective to determine whether patients presenting both peripheral nerve damage and migraine also exhibit symptoms of Asperger’s [etc.], offering a correlation that would offer preliminary corroboration of the defective-microglia-based “immune system disorder” theory for brain disorders.

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