Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Province Laboratory of Anesthetic and Analgesia Application Technology, Xuzhou Medicine University, Xuzhou, China.
Sci Rep. 2017 Jun 9;7(1):3124. doi: 10.1038/s41598-017-03590-3.
Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, IL-6) as well as imbalance of pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and sham-operated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype. Interestingly, higher serum levels of IL-1β and IL-6 in the rat with depression-like phenotype were normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine's antidepressant actions.
虽然疼痛常伴有抑郁，但对于导致疼痛和抑郁共病的个体差异的风险因素知之甚少。在这项研究中，我们研究了细胞因子和脑源性神经营养因子 (BDNF) 是否可能导致神经病理性疼痛引起的抑郁的个体差异。大鼠被随机进行神经保留结扎 (SNI) 或假手术。根据与抑郁相关的行为测试数据，SNI 大鼠被分为两组。具有抑郁样表型的大鼠表现出更高水平的促炎细胞因子（例如白细胞介素 (IL)-1β、IL-6），以及促炎/抗炎细胞因子失衡，与无抑郁样表型和假手术大鼠相比。具有抑郁样表型的大鼠前额叶皮层中的 BDNF 水平低于无抑郁样表型和假手术大鼠。单次给予氯胺酮可改善具有抑郁样表型的大鼠的抑郁样行为。有趣的是，具有抑郁样表型的大鼠单次给予氯胺酮后，血清中更高水平的 IL-1β 和 IL-6 得到了正常化。这些发现表明，炎症细胞因子和 BDNF 的改变可能导致神经病理性疼痛引起的抑郁，而血清细胞因子可能是氯胺酮抗抑郁作用的可预测生物标志物。
