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
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.