Emerging intervention of antidepressant with DMARD in non-cancerous nociceptive persistent pain associated depression in FCA induced rheumatoid arthritic rats

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund’s complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats.

类风湿关节炎（Rheumatoid arthritis, RA）是一种慢性炎症性疾病，可引发疼痛、全身并发症及过早死亡。抑郁症同样被证实为RA患者群体中存在的问题，且即便在控制疾病活动度后，该关联仍具有统计学显著性。本研究探究了抗抑郁药阿米替林（amitriptyline）与改善病情抗风湿药来氟米特（leflunomide）联合疗法，对完全弗氏佐剂（Freund’s complete adjuvant, FCA）诱导的类风湿关节炎伴疼痛相关性抑郁症模型大鼠的治疗效果。研究于大鼠FCA诱导关节炎造模9天后启动给药方案。抗关节炎活性通过足容积、负重能力、血液学、生化、血清学指标，以及胫跗关节的影像学分析与组织病理学检查进行评估；抗抑郁活性则采用强迫游泳实验、滚轴杆实验进行评估，并通过检测脑内神经递质（5-羟色胺与去甲肾上腺素）水平予以验证。研究结果表明，与关节炎模型对照组相比，来氟米特联合阿米替林可产生更为显著（p<0.001）的抗关节炎与抗抑郁作用；单独使用来氟米特仅能展现出显著（p<0.001）的抗关节炎活性。其中，来氟米特联合低剂量阿米替林的给药方案，在改善类风湿关节炎大鼠疼痛相关性抑郁症状方面效果更为突出。