Department of Pharmacology, Faculty of Medicine, Trakya University, 22030 Edirne, Turkey.
Neurosci Lett. 2011 Mar 10;491(1):23-5. doi: 10.1016/j.neulet.2010.12.063. Epub 2011 Jan 4.
Glutamate is the principal excitatory neurotransmitter in the central nervous system. Recent evidence suggests that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Moreover, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids, and reduce visceral and nerve injury-induced neuropathic nociceptive responses. The aim of this study is to observe the effect of a beta lactam antibiotic, ceftriaxone, on mechanical allodynia and mechanical hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindpaws. Mechanical allodynia was detected with an electronic aesthesiometer, and mechanical hyperalgesia was studied using the method of Randall-Selitto. With its higher doses, ceftriaxone (100, 200 mg/kg, i.p.) reduced both mechanical allodynia and hyperalgesia. Dihydrokainic acid (10 mg/kg, i.p.), a selective GLT-1 transporter inhibitor, reversed the anti-allodynic and anti-hyperalgesic effects of ceftriaxone, at doses that produced no effect on its own. Our results indicate that ceftriaxone exerts an antinociceptive effect in streptozocin-induced diabetic rats and GLT-1 activation by beta lactam antibiotics may be a promising option in the treatment of diabetic neuropathy.
谷氨酸是中枢神经系统中的主要兴奋性神经递质。最近的证据表明，β-内酰胺类抗生素通过增加谷氨酸转运体的表达提供神经保护作用。此外，这些抗生素已被证明可以预防阿片类药物的耐受和依赖的发展，并减少内脏和神经损伤引起的神经性疼痛反应。本研究的目的是观察β-内酰胺类抗生素头孢曲松对糖尿病大鼠机械性痛觉过敏和机械性痛觉超敏的影响。糖尿病是通过单次注射链脲佐菌素（50mg/kg，腹腔注射）产生的，这一过程导致后爪出现神经性疼痛行为。使用电子压痛计检测机械性痛觉过敏，使用 Randall-Selitto 法研究机械性痛觉超敏。头孢曲松（100、200mg/kg，腹腔注射）高剂量可降低机械性痛觉过敏和痛觉超敏。GLT-1 转运体选择性抑制剂二氢海因酸（10mg/kg，腹腔注射）逆转了头孢曲松的抗痛觉过敏和抗痛觉超敏作用，而其自身剂量则没有这种作用。我们的结果表明，头孢曲松在链脲佐菌素诱导的糖尿病大鼠中具有镇痛作用，β-内酰胺类抗生素通过激活 GLT-1 可能是治疗糖尿病性神经病的一种有前途的选择。
