PDF(Pubmed)
Abstract：
UNASSIGNED: Chronic peripheral neuropathic pain (PNP) is a debilitating condition that is associated with many types of injury/diseases, including diabetes mellitus. Patients with longstanding diabetes develop diabetic PNP (DPNP), which is resilient to currently available drugs. The underlying molecular mechanisms of DPNP are still illusive, but Kv7 channels that have been implicated in the pathogenesis of various types of chronic pain are likely to be involved. Indeed, using the streptozotocin (STZ) rat model of DPNP, we have previously shown that Kv7 activation with their non-selective activator retigabine attenuated neuropathic pain behavior suggesting that these channels are implicated in DPNP pathogenesis. Here, we evaluated, in the same STZ model, whether the more potent and more selective Kv7 channel openers flupirtine and ML213 attenuate STZ-induced pain hypersensitivity.
UNASSIGNED: Male Sprague Dawley rats (250-300 g) were used. The STZ model involved a single injection of STZ (60 mg/kg, i.p.). Behavioral testing for mechanical and heat pain sensitivity was performed using a dynamic plantar aesthesiometer and Hargreaves analgesiometer, respectively.
UNASSIGNED: STZ rats exhibited behavioral signs of mechanical and heat hypersensitivity as indicated by significant decreases in the mean paw withdrawal threshold (PWT) and mean paw withdrawal latency (PWL), respectively, at 35 days post-STZ treatment. Single injections of flupirtine (10 mg/kg, i.p.) and ML213 (5 mg/kg, i.p.) to STZ rats (35-days after STZ treatment) caused significant increases in the mean PWT, but not PWL, indicating attenuation of mechanical, but not heat hypersensitivity. Both flupirtine and ML213 were as effective as the positive control gabapentin (10/kg, i.p.), and their anti-allodynic effects were prevented by the Kv7 channel-specific blocker XE991 (3 mg/kg, i.p.).
UNASSIGNED: The findings suggest that Kv7 channels are involved in the mechanisms of mechanical but not heat hypersensitivity associated with DPNP, and that their activation may prove to be effective in alleviating DPNP symptoms.
UNASSIGNED: Male Sprague Dawley rats (250-300 g) were used. The STZ model involved a single injection of STZ (60 mg/kg, i.p.). Behavioral testing for mechanical and heat pain sensitivity was performed using a dynamic plantar aesthesiometer and Hargreaves analgesiometer, respectively.
UNASSIGNED: STZ rats exhibited behavioral signs of mechanical and heat hypersensitivity as indicated by significant decreases in the mean paw withdrawal threshold (PWT) and mean paw withdrawal latency (PWL), respectively, at 35 days post-STZ treatment. Single injections of flupirtine (10 mg/kg, i.p.) and ML213 (5 mg/kg, i.p.) to STZ rats (35-days after STZ treatment) caused significant increases in the mean PWT, but not PWL, indicating attenuation of mechanical, but not heat hypersensitivity. Both flupirtine and ML213 were as effective as the positive control gabapentin (10/kg, i.p.), and their anti-allodynic effects were prevented by the Kv7 channel-specific blocker XE991 (3 mg/kg, i.p.).
UNASSIGNED: The findings suggest that Kv7 channels are involved in the mechanisms of mechanical but not heat hypersensitivity associated with DPNP, and that their activation may prove to be effective in alleviating DPNP symptoms.
摘要：
■慢性周围神经性疼痛（PNP）是一种使人衰弱的病症，与许多类型的损伤/疾病相关，包括糖尿病。长期糖尿病患者发展为糖尿病PNP（DPNP），对目前可用的药物有弹性。DPNP的潜在分子机制仍然是虚幻的，但与各种类型慢性疼痛发病机制有关的Kv7通道可能参与其中。的确,采用链脲佐菌素(STZ)DPNP大鼠模型,我们之前已经证明Kv7激活及其非选择性激活剂瑞替加滨可减弱神经性疼痛行为,提示这些通道与DPNP发病机制有关.这里,我们评估,在同一个STZ模型中，更有效和更有选择性的Kv7通道开放剂氟吡汀和ML213是否减弱STZ诱导的疼痛超敏反应。
■使用雄性SpragueDawley大鼠(250-300g)。STZ模型包括单次注射STZ(60mg/kg，i.p.）。使用动态足底麻醉仪和Hargreaves镇痛仪进行机械和热痛敏感性的行为测试，分别。
■STZ大鼠表现出机械和热超敏反应的行为体征，这表明平均爪退缩阈值（PWT）和平均爪退缩潜伏期（PWL）显着降低，分别,在STZ治疗后35天。单次注射氟吡汀（10mg/kg，i.p.）和ML213（5mg/kg，i.p.）对STZ大鼠（STZ治疗后35天）引起平均PWT显着增加，但不是PWL,指示机械衰减，但不是热过敏。氟吡汀和ML213均与阳性对照加巴喷丁（10/kg，i.p.),Kv7通道特异性阻断剂XE991（3mg/kg，i.p.）。
■研究结果表明，Kv7通道参与了与DPNP相关的机械而不是热超敏反应的机制，并且它们的激活可能被证明在缓解DPNP症状方面是有效的。
■使用雄性SpragueDawley大鼠(250-300g)。STZ模型包括单次注射STZ(60mg/kg，i.p.）。使用动态足底麻醉仪和Hargreaves镇痛仪进行机械和热痛敏感性的行为测试，分别。
■STZ大鼠表现出机械和热超敏反应的行为体征，这表明平均爪退缩阈值（PWT）和平均爪退缩潜伏期（PWL）显着降低，分别,在STZ治疗后35天。单次注射氟吡汀（10mg/kg，i.p.）和ML213（5mg/kg，i.p.）对STZ大鼠（STZ治疗后35天）引起平均PWT显着增加，但不是PWL,指示机械衰减，但不是热过敏。氟吡汀和ML213均与阳性对照加巴喷丁（10/kg，i.p.),Kv7通道特异性阻断剂XE991（3mg/kg，i.p.）。
■研究结果表明，Kv7通道参与了与DPNP相关的机械而不是热超敏反应的机制，并且它们的激活可能被证明在缓解DPNP症状方面是有效的。
