| Sujet | calcium; divalent cation; hydroxy 1,12 pyrazolinominocycline; magnesium ion; minocycline; prostaglandin E2; pyrazoline derivative; toll like receptor 2; toll like receptor 4; unclassified drug; allodynia; animal cell; animal experiment; animal model; animal tissue; antibacterial activity; antiinflammatory activity; cell viability; chelation; female; genetic transfection; in vitro study; kidney cell; microglia; mouse; nerve injury; neuropathic pain; sham procedure; single drug dose; treatment duration; treatment outcome; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Dinoprostone; Female; Hyperalgesia; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microglia; Minocycline; Neuralgia; Physical Stimulation; Rats; Rats, Wistar; Sciatic Nerve; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; Touch |
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| Résumé | Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca2+; Mg2+) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75mg/kg, 47.50mg/kg or 95.00mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines. © 2013 Elsevier Ireland Ltd. |
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