Objective To investigate the effects of nitric oxide （NO） with different doses on modulation of inflammatory pain, and its possible mechanisms.Methods NO precursor L-arginine （L-Arg） was intrathecally administered...Objective To investigate the effects of nitric oxide （NO） with different doses on modulation of inflammatory pain, and its possible mechanisms.Methods NO precursor L-arginine （L-Arg） was intrathecally administered in rats at a dose of 10 μg per day （low dose group） or 250μg per day （high dose group） for a succession of 4 d.Normal saline was applied as a control.Then the rats were subcutaneously injected with formalin （100μL,2%） into the right hindpaw,and the nociceptive behavioral responses within 1 h were observed.At 4 h after formalin injection,neuronal NO synthase （nNOS） and c-Fos expression in spinal dorsal horn was examined with immunocytochemistry method.Results The subcutaneous injection of formalin evoked biphasic behaviors of licking or biting the injected paw.There was no difference in acute phase of formalin test among the 3 groups,while in tonic phase,the licking and biting time,and the protein levels of nNOS and c-Fos in spinal dorsal horn were significantly decreased in low dose group and increased in high dose group,compared with those in control group.Conclusion These results suggest that multiple administration of NO with different doses may produce different effects.On one hand,the low dose of NO can induce antinociception.On the other hand,the high dose of NO can induce pronociception.展开更多
Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high...Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a highfat diet, we found that:(1) the acute thermal pain sensory threshold did not change in obese mice;(2) the model obese mice had fewer nociceptive responses in formalininduced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation;(3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice,indicating the dysmodulation of topical leptin–leptin receptor signaling in these mice; and(4) leptin–leptin receptor signaling-deficient mice(ob/ob and db/db) or leptin–leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wildtype mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin–leptin receptor pathway could be a peripheral target against acute inflammatory pain.展开更多
目的 探讨大鼠福尔马林致痛的可能机制。方法 雄性 SD大鼠 64只 ,随机分为对照组 ( NS组、福尔马林对照组 )和实验组 ( L a F组、L n F组 )。 NS组为正常对照组 ,L a F组、L n F组在同福尔马林对照组处理前分别给予 L -精氨酸 ( L - A...目的 探讨大鼠福尔马林致痛的可能机制。方法 雄性 SD大鼠 64只 ,随机分为对照组 ( NS组、福尔马林对照组 )和实验组 ( L a F组、L n F组 )。 NS组为正常对照组 ,L a F组、L n F组在同福尔马林对照组处理前分别给予 L -精氨酸 ( L - Arg) ,L - NG-硝基精氨酸甲酯 ( L - NAME)鞘内注射 ,在福尔马林处理后 1/ 2 h、0～ 1h分别检测大鼠脊髓 NOS及 Fos的表达及观察大鼠的行为学表现。结果 福尔马林对照组的缩腿舔爪时间长于 NS组、脊髓的NOS及 Fos表达显著强于 NS组 ,预先给予 L - Arg或 L - NAME分别能加强或抑制以上作用。结论 福尔马林致痛能引起大鼠脊髓背角 NO的释放 ,诱导展开更多
文摘Objective To investigate the effects of nitric oxide （NO） with different doses on modulation of inflammatory pain, and its possible mechanisms.Methods NO precursor L-arginine （L-Arg） was intrathecally administered in rats at a dose of 10 μg per day （low dose group） or 250μg per day （high dose group） for a succession of 4 d.Normal saline was applied as a control.Then the rats were subcutaneously injected with formalin （100μL,2%） into the right hindpaw,and the nociceptive behavioral responses within 1 h were observed.At 4 h after formalin injection,neuronal NO synthase （nNOS） and c-Fos expression in spinal dorsal horn was examined with immunocytochemistry method.Results The subcutaneous injection of formalin evoked biphasic behaviors of licking or biting the injected paw.There was no difference in acute phase of formalin test among the 3 groups,while in tonic phase,the licking and biting time,and the protein levels of nNOS and c-Fos in spinal dorsal horn were significantly decreased in low dose group and increased in high dose group,compared with those in control group.Conclusion These results suggest that multiple administration of NO with different doses may produce different effects.On one hand,the low dose of NO can induce antinociception.On the other hand,the high dose of NO can induce pronociception.
基金supported by the National Natural Science Fundation of China(81473749,81371247,31600852,and 31421091)WuXi AppTec
文摘Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a highfat diet, we found that:(1) the acute thermal pain sensory threshold did not change in obese mice;(2) the model obese mice had fewer nociceptive responses in formalininduced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation;(3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice,indicating the dysmodulation of topical leptin–leptin receptor signaling in these mice; and(4) leptin–leptin receptor signaling-deficient mice(ob/ob and db/db) or leptin–leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wildtype mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin–leptin receptor pathway could be a peripheral target against acute inflammatory pain.
