促肾上腺皮质激素对慢性痛大鼠痛行为和海马内BDNF、CRF水平的影响

目的与方法:采用痛行为评分方法、免疫组化和原位杂交技术,观察促肾上腺皮质激素(ACTH)对完全福氏佐剂所致的关节炎大鼠海马内脑源性神经营养因子(BDNF)及其功能性受体trkB和促肾上腺皮质激素释放激素(CRH)水平的影响。结果:关节炎大鼠的痛行为评分显著高于正常对照组,同时注射侧对侧海马内BDNF免疫活性(IR)神经元、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数在注射佐剂后 2 4h显著高于正常对照组,而腹腔注射ACTH(2 5IU/kg或 12 5IU/kg)后,上述指标显著低于关节炎组;摘除双侧肾上腺后,腹腔注射ACTH的关节炎大鼠对侧海马内BDNF-IR、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数明显高于未摘除肾上腺的关节炎组。结论:海马内的BDNF和CRH参与慢性痛的调制,ACTH能抑制海马内BDNF和CRH的升高而产生镇痛作用,肾上腺对ACTH发挥其功能起决定性作用.

Effect of ACTH on pain behavior and the level of brain-derived neurotrophic factor and corticotropin-releasing hormone in the hippocampus of rats with chronic pain

AIM: To observe the effect of adrenocorticotropic hormone(ACTH) on the levels of brain-derived neurotrophic factor (BDNF), trkB and corticotropin-releasing hormone(CRH) in the hippocampus of arthritic rats.METHODS: The BDNF immunoreactivity (IR) and CRH-positive neurons were stained with immunohistochemistry and in situ hybridization methods, respectively.RESULTS: The BDNF-IR, CRH mRNA-positive neurons in the contralateral hippocampus of the arthritic rats were increased significantly, which was decreased markedly by intraperitoneal injection of ACTH. However, the effect of ACTH was attenuated after adrenalectomy (ADX).CONCLUSION: These results suggest that BDNF and CRH in the hippocampus of arthritic rats were involved in the modulation of chronic pain, ACTH produced its analgesic effect by inhibiting the increase in BDNF and CRF level. Adrenal is critical to the analgesic action of ACTH.