Objectives

Functional changes in the autonomic nervous system may help explain variability in the progression of knee osteoarthritis (OA). Thus, the objective of this study was to evaluate autonomic nervous system shifts, measured via heart rate response variables, in rat knee joint injury and OA models.

Methods

Cardiovascular characteristics were measured at baseline and bi-weekly for 8 weeks after skin incision, medial collateral ligament transection (MCLT), or MCLT+medial meniscus transection (MCLT+MMT). Heart rate was also assessed during a mild stressor (elevated maze). At endpoint, cardiovascular responses to mechanical knee stimuli were evaluated, as well as responses to 1-phenylbiguanide, a 5HT_3A receptor agonist with reported ability to stimulate vagal responses.

Results

During low activity, a slower heart rate occurred in MCLT (299 ± 10 bpm) and MCLT+MMT (310 ± 10 bpm) animals compared to controls (325 ± 10 bpm). Furthermore, patellar ligament mechanical stimuli produced an immediate decrease in heart rate and blood pressure in all groups. Finally, a larger drop in heart rate was observed in MCLT (252 ± 40 bpm) and MCLT+MMT (263 ± 49 bpm) following administration of 1-phenylbiguanide compared to skin incision (168 ± 45 bpm).

Conclusions

Acute mechanical stimulation of the patellar ligament produced drops in heart rate, suggesting a possible joint-brain connection that modulates autonomic responses. With both joint injury, cardiac vagal activation was altered in response to pharmacological stimulation, with chronic longitudinal heart rate reduction. These data provide some preliminary evidence of potential functional shifts in autonomic nervous system function in models of joint injury and OA.

中文翻译：

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心血管功能的测量表明在雄性 Lewis 大鼠手术诱导关节损伤后自主神经系统失调

目标

自主神经系统的功能变化可能有助于解释膝骨关节炎 (OA) 进展的变异性。因此，本研究的目的是评估大鼠膝关节损伤和 OA 模型中的自主神经系统变化，通过心率反应变量测量。

方法

在皮肤切开、内侧副韧带横断 (MCLT) 或 MCLT+内侧半月板横断 (MCLT+MMT) 后的 8 周内，在基线和每两周测量一次心血管特征。在轻度应激源（高架迷宫）期间也评估了心率。在终点处，评估了对膝关节机械刺激的心血管反应，以及对 1-苯基双胍（一种据报道能够刺激迷走神经反应的5HT _{3A受体激动剂）的反应。}

结果

在低活动期间，与对照组 (325 ± 10 bpm) 相比，MCLT (299 ± 10 bpm) 和 MCLT+MMT (310 ± 10 bpm) 动物的心率较慢。此外，髌韧带机械刺激使所有组的心率和血压立即下降。最后，与皮肤切口 (168 ± 45 bpm) 相比，在 MCLT (252 ± 40 bpm) 和 MCLT + MMT (263 ± 49 bpm) 中观察到心率下降幅度更大。

结论

对髌韧带的急性机械刺激导致心率下降，表明可能存在调节自主神经反应的关节-大脑连接。对于这两种关节损伤，心脏迷走神经激活因药理刺激而改变，慢性纵向心率降低。这些数据为关节损伤和 OA 模型中自主神经系统功能的潜在功能转变提供了一些初步证据。