OBJECTIVES The appearance of endogenous tyrosine hydroxylase-positive cells (TH+ cells) in collagen-induced arthritis was associated with an anti-inflammatory effect. Here we investigated putative anti-inflammatory and antinociceptive effects of the transfer of induced, bone marrow stem cell-derived TH+ cells (iTH+ cells) on murine antigen-induced arthritis (AIA). METHODS Bone marrow-derived stem cells were differentiated into iTH+ cells. These cells were transferred to mice immunized against methylated bovine serum albumin (mBSA) 2 days before AIA was induced by injection of mBSA into one knee joint. In AIA control mice and iTH+-treated mice the severity of AIA, pain-related behavior, humoral and cellular responses, and the invasion of macrophages into the dorsal root ganglia were assessed. RESULTS The intravenous transfer of iTH+ cells before AIA induction did not cause a sustained suppression of AIA severity but significantly reduced inflammation-evoked pain-related behavior. The iTH+ cells used for transfer exhibited enormous production of interleukin-4. A major difference between AIA control mice and iTH+-treated AIA mice was a massive invasion of the dorsal root ganglia by iNOS-negative, arginine 1-positive macrophages corresponding to an M2 phenotype. The differences in other cellular and humoral immune parameters such as release of cytokines from stimulated lymphocytes between AIA control mice and iTH+-treated mice were small. CONCLUSIONS The transfer of iTH+ cells may cause a long-lasting reduction of arthritis-induced pain even if it does not ameliorate inflammation. The invasion of M2 macrophages into the dorsal root ganglia is likely to be an important mechanism of antinociception.

中文翻译：

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一种治疗炎症性疼痛的有前途的新方法：干细胞衍生的酪氨酸羟化酶阳性细胞的转移。

目的胶原诱导的关节炎中内源性酪氨酸羟化酶阳性细胞（TH +细胞）的出现与抗炎作用有关。在这里，我们研究了诱导的骨髓干细胞来源的TH +细胞（iTH +细胞）转移对鼠抗原诱导的关节炎（AIA）的推定抗炎和镇痛作用。方法将骨髓干细胞分化为iTH +细胞。在将mBSA注射到一个膝关节中诱发AIA之前2天，将这些细胞转移到对甲基化牛血清白蛋白（mBSA）进行了免疫的小鼠上。在AIA对照小鼠和iTH +治疗的小鼠中，评估了AIA的严重程度，疼痛相关行为，体液和细胞反应以及巨噬细胞侵入背根神经节。结果AIA诱导前iTH +细胞的静脉转移并未引起AIA严重程度的持续抑制，但显着降低了炎症引起的疼痛相关行为。用于转移的iTH +细胞表现出大量的白介素4产生。AIA对照小鼠和iTH +治疗的AIA小鼠之间的主要区别是对应于M2表型的iNOS阴性精氨酸1阳性巨噬细胞对背根神经节的大规模侵袭。在AIA对照小鼠和iTH +治疗的小鼠之间，其他细胞和体液免疫参数（例如从刺激的淋巴细胞释放细胞因子）的差异很小。结论iTH +细胞的转移可能会导致关节炎引起的疼痛的长期减轻，即使它不会减轻炎症。