Bonaterra Gabriel Alejandro, Then Hanna, Oezel Lisa, Schwarzbach Hans, Ocker Matthias, Thieme Kati, Di Fazio Pietro, Kinscherf Ralf
Anatomy und Cell Biology, Department of Medical Cell Biology, University of Marburg, Marburg, Hessen, Germany.
Institute for Surgical Research, Philipps University of Marburg, Marburg, Hessen, Germany.
PLoS One. 2016 Mar 17;11(3):e0151116. doi: 10.1371/journal.pone.0151116. eCollection 2016.
Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice.
Male and female ICS mice were kept under alternating temperature (4 °C/room temperature [22 °C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen-cooled isopentane or fixed for electron microscopy.
In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm(2)) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice.
The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or delayed. The sex-specificity of findings, which is not easily reconciled with the epidemiology of FM (female predominance), implicate that gastrocnemius muscle of male ICS mice should preferentially be used for future investigations with FM. Moreover, we suggest to investigate morphological and/or molecular alterations at different time-points (up to two weeks) after ICS.
纤维肌痛（FM）是一种慢性肌肉骨骼疼痛疾病，其特征为慢性广泛性疼痛和身体压痛，常伴有情感障碍，但其病因往往不明。根据最近的报道，身体和心理压力会引发纤维肌痛。为开发针对纤维肌痛的新疗法，需要建立并表征纤维肌痛的实验动物模型。利用包括间歇性冷应激（ICS）的纤维肌痛小鼠模型，我们推测ICS会导致小鼠骨骼肌发生形态学改变。
将雄性和雌性ICS小鼠置于交替温度（4℃/室温[22℃]）环境中；持续饲养在室温下的小鼠作为对照。处死后切除腓肠肌和比目鱼肌，并在液氮冷却的异戊烷中速冻或固定用于电子显微镜检查。
在雄性ICS小鼠的腓肠肌/比目鱼肌中，我们发现纤维横截面积（FCSA）分别下降了21.6%和33.
