A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.
A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.
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DOI：
10.1016/j.neulet.2013.03.014
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发表时间：
2013-05-24
影响因子：
2.5
通讯作者：
Moraes MF
中科院分区：
文献类型：
--
作者：
Bastos LF;Godin AM;Zhang Y;Jarussophon S;Ferreira BC;Machado RR;Maier SF;Konishi Y;de Freitas RP;Fiebich BL;Watkins LR;Coelho MM;Moraes MF
许多研究表明，米诺环素，一种抗菌四环素，抑制实验性疼痛。虽然米诺环素对疼痛缓解的积极作用表明临床使用此类药物可能证明是有益的，但米诺环素的抗生素作用和二价阳离子（Ca2 +; Mg2+）螯合作用减损了其潜在的效用。因此，我们测试了由非抗菌、非螯合米诺环素衍生物在神经性疼痛模型中诱导的抗异常性疼痛作用，并对其体外抗炎作用进行了初步研究。腹腔注射米诺环素（100 mg/kg）和12 S-羟基-1，12-吡唑啉米诺环素（PMIN; 23.75，47.50或95.00 mg/kg）可减轻小鼠坐骨神经慢性压迫性损伤引起的机械性异常性疼痛。PMIN减少LPS诱导的原代小胶质细胞培养物产生PGE2。转染人胚肾细胞以表达人Toll样受体2和4，并且通过分别用PAM 3CSK 4或LPS刺激的两种受体的信号传导受到米诺环素或PMIN的影响。重要的是，这些处理不影响细胞活力，如通过MTT测试评估的。总之，这些结果加强了四环素类诱导的抗炎和实验性疼痛抑制作用既不一定与抗菌活性也不一定与Ca2+螯合活性相关的证据。这项研究支持评估PMIN在神经性疼痛管理中的潜在有用性，因为其缺乏抗菌和Ca2+螯合活性可能比传统四环素类药物具有更大的安全性。
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 (100 mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75, 47.50 or 95.00 mg/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.
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影响因子：
3.3
作者：
Kim D;You B;Lim H;Lee SJ
通讯作者：
Lee SJ
影响因子：
7.6
作者：
GOLUB, LM;MCNAMARA, TF;RAMAMURTHY, NS
通讯作者：
RAMAMURTHY, NS
影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR
影响因子：
5
作者：
Bastos, Leandro Francisco S.;Merlo, Leonardo A.;Coelho, Marcio M.
通讯作者：
Coelho, Marcio M.
影响因子：
7.3
作者：
Bastos, L. F. S.;Angusti, A.;Coelho, M. M.
通讯作者：
Coelho, M. M.