Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland.
Int J Mol Sci. 2024 Oct 21;25(20):11323. doi: 10.3390/ijms252011323.
Research has shown that obesity is a low-grade inflammatory disease that is often associated with comorbidities, such as diabetes and chronic pain. Recent data have indicated that chemokines may play a role in these conditions due to their pronociceptive and chemotactic properties, which promote hypersensitivity and inflammation. Accumulating evidence suggests that CCR2, CCR5, and their ligands (CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11 CCL12, and/or CCL13) play a role in rodent models of pain and obesity, as well as in patients with diabetes and obesity. It was proven that the blockade of CCR2 and CCR5, including the simultaneous blockade of both receptors by dual antagonists, effectively reduces hypersensitivity to thermal and mechanical stimuli in chronic pain states, including diabetic neuropathy. The present review discusses these chemokine receptors and the role of their ligands in diabetes and obesity, as well as their involvement in diabetic neuropathy and obesity-induced hypersensitivity.
研究表明，肥胖是一种低度炎症性疾病，常伴有糖尿病和慢性疼痛等合并症。最近的数据表明，趋化因子可能因其致痛和趋化特性而在这些疾病中发挥作用，这些特性促进了过敏和炎症。越来越多的证据表明，CCR2、CCR5 及其配体（CCL2、CCL3、CCL4、CCL5、CCL7、CCL8、CCL11、CCL12 和/或 CCL13）在肥胖和糖尿病患者的疼痛和肥胖的啮齿动物模型中发挥作用。事实证明，CCR2 和 CCR5 的阻断，包括双重拮抗剂对这两种受体的同时阻断，可有效减轻慢性疼痛状态（包括糖尿病性神经病）对热和机械刺激的过敏反应。本文综述了这些趋化因子受体及其配体在糖尿病和肥胖中的作用，以及它们在糖尿病性神经病和肥胖诱导的过敏反应中的作用。
