Measures of cardiovascular function suggest autonomic nervous system dysregulation after surgical induction of joint injury in the male Lewis rat

Yeater, Taylor; Zubcevic, Jasenka; Allen, Kyle D.

doi:10.1016/j.joca.2021.12.008

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…In contrast to our current findings, we previously conducted a similar study using male Lewis rats [ 15 ] where heart rate responses to intravenous phenybiguanide administration did not significantly differ between OA and non-OA. However, the Lewis rat has a dysfunctional hypothalamic-pituitary-adrenal axis (HPA axis), which can confound autonomic measures [ 31 ].…”

Section: Discussioncontrasting

confidence: 99%

“…Endpoint measures of cardiovascular function were assessed as previously described [ 15 ]. Rats were anesthetized with isoflurane, and body temperature was maintained at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Disruptions to ANS balance have been implicated in multiple disease states, including chronic pain [ 9 – 11 ], rheumatoid arthritis [ 12 , 13 ], and hypertension [ 14 ]. Prior work from our group has demonstrated cardiovascular changes in a rat surgical model of OA [ 15 ]. Here, joint injury in male Lewis rats caused greater reductions in heart rate with pharmacological activation of the vagus nerve—the major parasympathetic nerve of the body.…”

Section: Introductionmentioning

confidence: 99%

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Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner

et al. 2023

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Background Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension. Methods Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n = 7–8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9–10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections. Results In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OA p < 0.001) and normotensive (OA vs. non-OA p < 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p = 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p = 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p < 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p = 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensive p = 0.018) and sham (hypertensive vs. normotensive p < 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensive p = 0.005). Conclusion These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.

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Section: Discussioncontrasting

confidence: 99%

“…Endpoint measures of cardiovascular function were assessed as previously described [ 15 ]. Rats were anesthetized with isoflurane, and body temperature was maintained at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner

et al. 2023

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“…The onset of peripheral and central sensitization promotes and maintains OA-related pain and may perturb autonomic nervous system (ANS) function [ 9 ]. A dysfunctional ANS has been suggested in multiple chronic musculoskeletal diseases [ 10 ] and even in a preclinical model of OA [ 11 ]. Due to the role of the ANS in regulating neuroimmune health, perturbations in its function could impact joint health.…”

Section: Introductionmentioning

confidence: 99%

Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

Cruz,

Yeater,

Griffith

et al. 2024

Osteoarthritis and Cartilage Open

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“…Preliminary data from animal studies suggest a potential shift of the autonomic nervous system measured via heart rate response variables also in OA [24,25]. However, to date there is no data available investigating the autonomic tone in OA patients or autonomic alterations and their association with clinical symptoms such as pain in different stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance

Sohn,

Assar,

Kaufhold

et al. 2024

J Transl Med

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Background Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements. Methods Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed. Results GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level. Conclusions This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option. Graphical abstract

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Measures of cardiovascular function suggest autonomic nervous system dysregulation after surgical induction of joint injury in the male Lewis rat

Cited by 5 publications

References 44 publications

Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner

Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner

Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance

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