J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Osteoarthritis Cartilage. 2022 Apr;30(4):586-595. doi: 10.1016/j.joca.2021.12.008. Epub 2022 Jan 10.
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.
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 receptor agonist with reported ability to stimulate vagal responses.
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).
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.
自主神经系统的功能变化可能有助于解释膝关节骨关节炎（OA）进展的可变性。因此，本研究旨在评估通过心率反应变量测量的大鼠膝关节损伤和 OA 模型中自主神经系统的变化。
在皮肤切口、内侧副韧带切断术（MCLT）或 MCLT+内侧半月板切断术（MCLT+MMT）后 8 周内，基线和每两周测量心血管特征。心率也在轻度应激（高架迷宫）期间进行评估。在终点，评估了机械膝关节刺激的心血管反应，以及对 1-苯基双胍的反应，1-苯基双胍是一种 5HT 受体激动剂，据报道具有刺激迷走神经反应的能力。
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，所有组的机械刺激髌韧带都会立即导致心率和血压下降。最后，与皮肤切口（168±45 bpm）相比，MCLT（252±40 bpm）和 MCLT+MMT（263±49 bpm）中观察到心率下降更大。
髌韧带的急性机械刺激会导致心率下降，这表明可能存在调节自主反应的关节-大脑连接。在关节损伤的情况下，心脏迷走神经激活对药物刺激的反应发生改变，导致慢性纵向心率降低。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变化提供了一些初步证据。
