Department of Anaesthesiology, The University of Hong Kong, HKSAR, China.
Life Sci. 2012 Oct 15;91(13-14):618-22. doi: 10.1016/j.lfs.2012.06.038. Epub 2012 Jul 20.
Endothelin-1 (ET-1) has been suggested to be involved in different types of pain due to its neuromodulatory nature. However, its role in inflammatory pain processing, specifically the origin-specific effect, has not yet been clearly defined. Therefore, the aim of this study is to determine the role of cell-type specific ET-1 induction in the modulation of inflammatory pain processing.
The current study assesses the effects of ET-1 over-expression specifically targeted to astrocytes (GET-1) or endothelial cells (TET-1) on the expression of pain-like behaviors induced by a model of inflammatory pain, consisting of a formalin injection into the hind paw.
The baseline sensitivity thresholds of GET-1 and TET-1 mice to the response elicited by tactile and radiant heat stimulation were similar to those observed in age-matched non-transgenic (NTg) controls. Relative to the NTg controls, GET-1 mice displayed a marked decrease in pain-like behavioral responses during the second phase of formalin-induced pain (i.e., 15-20 min after injection), whereas the responses elicited in TET-1 mice were unaltered. The levels of mRNA encoding adrenomedullin, calcitonin gene-related peptide and calcitonin-like receptor were elevated in the spinal cord of saline-injected GET-1 mice compared to those of NTg mice.
The current results support a suppressor role for astrocyte-derived ET-1 in inflammatory pain and suggest that the study of GET-1 mice might provide mechanistic insights for improving the treatment of inflammatory pain.
由于内皮素-1（ET-1）具有神经调节性质，因此它被认为参与了不同类型的疼痛。然而，其在炎症性疼痛处理中的作用，特别是其起源特异性效应，尚未得到明确界定。因此，本研究旨在确定细胞类型特异性 ET-1 诱导在炎症性疼痛处理中的调节作用。
本研究评估了 ET-1 特异性过表达针对星形胶质细胞（GET-1）或内皮细胞（TET-1）对炎症性疼痛模型诱导的疼痛样行为表达的影响，该模型包括在后爪注射福尔马林。
GET-1 和 TET-1 小鼠对触觉和辐射热刺激引起的反应的基线敏感阈值与同龄非转基因（NTg）对照相似。与 NTg 对照相比，GET-1 小鼠在福尔马林诱导的疼痛的第二阶段（即注射后 15-20 分钟）表现出明显减少的疼痛样行为反应，而 TET-1 小鼠的反应未改变。与 NTg 小鼠相比，在盐水注射的 GET-1 小鼠的脊髓中，编码肾上腺髓质素、降钙素基因相关肽和降钙素样受体的 mRNA 水平升高。
目前的结果支持星形胶质细胞衍生的 ET-1 在炎症性疼痛中的抑制作用，并表明 GET-1 小鼠的研究可能为改善炎症性疼痛的治疗提供机制见解。
