PMID:18215468

Citation	Scholz, J, Abele, A, Marian, C, Häussler, A, Herbert, TA, Woolf, CJ and Tegeder, I (2008) Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats. Pain 138:130-42
Abstract	Peripheral nerve injuries that provoke neuropathic pain are associated with microglial activation in the spinal cord. We have investigated the characteristics of spinal microglial activation in three distinct models of peripheral neuropathic pain in the rat: spared nerve injury (SNI), chronic constriction injury, and spinal nerve ligation. In all models, dense clusters of cells immunoreactive for the microglial marker CD11b formed in the ipsilateral dorsal horn 7 days after injury. Microglial expression of ionised calcium binding adapter molecule 1 (Iba1) increased by up to 40% and phosphorylation of p38 mitogen-activated protein kinase, a marker of microglial activity, by 45%. Expression of the lysosomal ED1-antigen indicated phagocytic activity of the cells. Unlike the peripheral nerve lesions, rhizotomy produced only a weak microglial reaction within the spinal gray matter but a strong activation of microglia and phagocytes in the dorsal funiculus at lumbar and thoracic spinal cord levels. This suggests that although degeneration of central terminals is sufficient to elicit microglial activation, it does not account for the inflammatory response in the dorsal horn after peripheral nerve injury. Early intrathecal treatment with low-dose methotrexate, beginning at the time of injury, decreased microglial activation, reduced p38 phosphorylation, and attenuated pain-like behavior after SNI. In contrast, systemic or intrathecal delivery of the glucocorticoid dexamethasone did not inhibit the activation of microglia or reduce pain-like behavior. We confirm that microglial activation is crucial for the development of pain after nerve injury, and demonstrates that suppression of this cellular immune response is a promising approach for preventing neuropathic pain.
Links	PubMed PMC2536692 Online version:10.1016/j.pain.2007.11.019
Keywords	Animals; Behavior, Animal/drug effects; Immunosuppressive Agents/administration & dosage; Male; Methotrexate/administration & dosage; Microglia/drug effects; Microglia/immunology; Neuralgia/etiology; Neuralgia/immunology; Neuralgia/pathology; Neuralgia/prevention & control; Peripheral Nerve Injuries; Peripheral Nerves/immunology; Rats; Rats, Sprague-Dawley; Spinal Cord/drug effects; Spinal Cord/immunology; Spinal Cord/pathology; Treatment Outcome
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