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.
- “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.