Systemic Lipopolysaccharide-Induced Pain Sensitivity and Spinal Inflammation Were Reduced by Minocycline in Neonatal Rats
Systemic Lipopolysaccharide-Induced Pain Sensitivity and Spinal Inflammation Were Reduced by Minocycline in Neonatal Rats
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DOI：
10.3390/ijms19102947
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发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Fan, Lir-Wan
中科院分区：
文献类型：
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作者：
Hsieh, Cheng-Ta;Lee, Yih-Jing;Fan, Lir-Wan
在这项研究中，我们研究了米诺环素，一个假定的抑制小胶质细胞活化，对全身性脂多糖（LPS）诱导的脊髓炎症，异常性疼痛，痛觉过敏的新生大鼠的影响。腹膜内（i. p.）在出生后第5天（P5）的大鼠幼崽中进行LPS（2 mg/kg）或无菌盐水的注射，并在第5天（P5）的大鼠幼崽中施用米诺环素（45 mg/kg）或载体（磷酸盐缓冲盐水; PBS）（i. p.）注射LPS后5 min。进行von Frey细丝和甩尾测试以确定机械异常性疼痛（由无害刺激引起的疼痛感觉，例如，轻触）和热痛觉过敏（一种温度感知改变的情况），并在给药后24小时检查脊髓炎症。全身LPS给药导致新生大鼠von Frey细丝测试中的触觉阈值和甩尾测试中的疼痛反应潜伏期降低。LPS刺激24 h后，脊髓内小胶质细胞和星形胶质细胞的活化、促炎细胞因子白细胞介素-1（IL-1）、环氧合酶-2（考克斯-2）和前列腺素E2（PGE 2）的水平升高。米诺环素治疗显著减弱LPS诱导的异常性疼痛，痛觉过敏，脊髓小胶质细胞的增加，星形胶质细胞活化，以及新生大鼠IL-1，考克斯-2和PGE 2水平升高。这些结果表明，米诺环素提供保护，防止新生儿全身性LPS刺激诱导的疼痛敏感性增强（异常性疼痛和痛觉过敏），和保护作用可能与其能力，以减弱LPS诱导的小胶质细胞活化，和水平的IL-1，考克斯-2，和前列腺素E2在新生大鼠脊髓。
In this study, we investigated the effects of minocycline, a putative suppressor of microglial activation, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation, allodynia, and hyperalgesia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups and minocycline (45 mg/kg) or vehicle (phosphate buffer saline; PBS) was administered (i.p.) 5 min after LPS injection. The von Frey filament and tail-flick tests were performed to determine mechanical allodynia (a painful sensation caused by innocuous stimuli, e.g., light touch) and thermal hyperalgesia (a condition of altered perception of temperature), respectively, and spinal cord inflammation was examined 24 h after the administration of drugs. Systemic LPS administration resulted in a reduction of tactile threshold in the von Frey filament tests and pain response latency in the tail-flick test of neonatal rats. The levels of microglia and astrocyte activation, pro-inflammatory cytokine interleukin-1 (IL-1), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the spinal cord of neonatal rats were increased 24 h after the administration of LPS. Treatment with minocycline significantly attenuated LPS-induced allodynia, hyperalgesia, the increase in spinal cord microglia, and astrocyte activation, and elevated levels of IL-1, COX-2, and PGE2 in neonatal rats. These results suggest that minocycline provides protection against neonatal systemic LPS exposure-induced enhanced pain sensitivity (allodynia and hyperalgesia), and that the protective effects may be associated with its ability to attenuate LPS-induced microglia activation, and the levels of IL-1, COX-2, and PGE2 in the spinal cord of neonatal rats.