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首页> 外文期刊>Frontiers in Neuropharmacology >The Benzimidazole Derivatives, B1 (N-[(1H-Benzimidazol-2-yl)Methyl]-4-Methoxyaniline) and B8 (N-{4-[(1H-Benzimidazol-2-yl)Methoxy]Phenyl}Acetamide) Attenuate Morphine-Induced Paradoxical Pain in Mice
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The Benzimidazole Derivatives, B1 (N-[(1H-Benzimidazol-2-yl)Methyl]-4-Methoxyaniline) and B8 (N-{4-[(1H-Benzimidazol-2-yl)Methoxy]Phenyl}Acetamide) Attenuate Morphine-Induced Paradoxical Pain in Mice

机译：苯并咪唑衍生物B1（N-[（1H-苯咪唑-2-基）甲基] -4-甲氧基苯胺）和B8（N- {4-[（1H-苯咪唑-2-基）甲氧基]苯基}乙酰胺）减弱吗啡引起的小鼠悖论性疼痛

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Despite being routinely used for pain management, opioids use is limited due to adverse effects such as development of tolerance and paradoxical pain including thermal hyperalgesia and mechanical allodynia. Evidence indicates that continued morphine administration causes increased expression of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α). The objectives of the present study were to determine the effects of B1 (N-[(1H-benzimidazol-2-yl)methyl]-4-methoxyaniline) and B8 (N-{4-[(1H-benzimidazol-2-yl)methoxy]phenyl}acetamide), benzimidazole derivatives, on thermal nociception and mechanical allodynia during repeated morphine (intraperitoneal; 5mg/kg twice daily for 6 days)-induced paradoxical pain and TNF-α expression in spinal cord in mice. Our data indicate that administration of benzimidazole derivatives attenuated morphine-induced thermal hyperalgesia and mechanical allodynia. Benzimidazole derivatives also reduced TNF-α expression in mice. Taken together, these results suggest that benzimidazole derivatives might be useful for the treatment of neuroinflammatory consequences of continued morphine-administration and could be potential drug candidates for the management of opioid-induced paradoxical pain.
机译：尽管常规使用阿片类药物来治疗疼痛，但由于不良反应，例如耐受性的发展和自相矛盾的疼痛（包括热痛觉过敏和机械性异常性疼痛），阿片类药物的使用受到限制。有证据表明，继续服用吗啡会导致促炎性介质（如肿瘤坏死因子-α（TNF-α））的表达增加。本研究的目的是确定B1（N-[（1H-苯并咪唑-2-基）甲基] -4-甲氧基苯胺）和B8（N- {4-[（1H-苯并咪唑-2-基）甲氧基]苯基}乙酰胺），苯并咪唑衍生物，在反复吗啡（腹膜内; 5mg / kg，每天两次，连续6天）引起的热伤害和机械性异常性疼痛中，引起小鼠脊髓悖论性疼痛和TNF-α表达。我们的数据表明，苯并咪唑衍生物的给药减弱了吗啡诱导的热痛觉过敏和机械性异常性疼痛。苯并咪唑衍生物还降低了小鼠的TNF-α表达。综上所述，这些结果表明，苯并咪唑衍生物可能对持续服用吗啡的神经炎性后果的治疗有用，并且可能是治疗阿片类药物引起的悖论性疼痛的潜在候选药物。

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