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Pain ; 137(1): 182-201, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18160218

RESUMO

Neuroinflammatory and neuroimmune mechanisms, as exemplified by infiltrating immune cells and activation of resident endothelial/glial cells, respectively, are known to be involved in the establishment and maintenance of chronic pain. An immune system pathway that may be involved in the activation of both immune and glial cells is complement. The complement pathway is made up of a large number of distinct plasma proteins which react with one another to opsonize pathogens and induce a series of inflammatory responses to help fight infection. Cleaved products and complexes produced by complement activation are responsible for a range of effects including mediation of immune infiltration, activation of phagocytes, opsonization/lysis of pathogens and injured cells, and production of vasoactive amines such as histamine and serotonin. Gene-expression microarray-analysis performed on the rat spinal nerve ligation (SNL) model of neuropathic pain revealed that multiple complement components including the C1 inhibitor, C1q alpha, beta, and gamma, C1r, C1s, C2, C3, C4, C7, and factors B, D, H, and P, were up-regulated while DAF was down-regulated. Regulation of C3 and DAF was confirmed by real-time RT-PCR and in situ hybridization. To test the hypothesis that complement plays a role in neuropathic pain, SNL rats were treated with cobra venom factor (CVF) to deplete plasma of complement component C3. Pain behavior was significantly attenuated in SNL rats treated with CVF as was complement activity at the ipsilateral dorsal root ganglia. Our results suggest the complement pathway might be a novel target for the development of neuropathic pain therapeutics.


Assuntos
Ativação do Complemento/fisiologia , Modelos Animais de Doenças , Neuralgia/imunologia , Neuralgia/fisiopatologia , Nervos Espinhais/fisiologia , Animais , Ativação do Complemento/genética , Ligadura , Neuralgia/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/fisiologia , Ratos , Nervos Espinhais/imunologia , Nervos Espinhais/patologia
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