Depressing interleukin-1ß contributed to the synergistic effects of tramadol and minocycline on spinal nerve ligation-induced neuropathic pain.
Neurosignals
; 22(1): 30-42, 2014.
Article
em En
| MEDLINE
| ID: mdl-24157594
Our previous study indicated that coadministration of tramadol and minocycline exerted synergistic effects on spinal nerve ligation (SNL)-induced neuropathic mechanical allodynia. However, the underlying mechanisms are still unclear. Recent reports indicated that spinal proinflammatory factor interleukin-1ß (IL-1ß) contributed to the development of neuropathic pain and the positive feedback communication between neuron and glia. Therefore, the present research is to confirm whether spinal IL-1ß-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain. Real-time RT-PCR demonstrated IL-1ß up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration. Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication. Meanwhile, intrathecal administration of p38 inhibitor SB203580 markedly alleviated mechanical allodynia whilst reducing IL-1ß and Fos expression induced by SNL. Moreover, intrathecal neutralized antibody of IL-1ß could depress SNL-induced mechanical allodynia and Fos expression. These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1ß-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nervos Espinhais
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Tramadol
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Interleucina-1beta
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Analgésicos
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Minociclina
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Neuralgia
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article