Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis

Cruz, Carlos Janssen Gomes da; Dewberry, L. Savannah; Otto, Kevin J.; Allen, Kyle D.

doi:10.1007/s11926-022-01094-2

Cited by 7 publications

(5 citation statements)

References 117 publications

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“…14 It has also been postulated that neuromodulation with bioelectronic medicine therapies such as DRG-S that target the autonomic nervous system may be able to treat osteoarthritis-related pain and pathogenesis by reducing related neurogenic inflammation and preventing maladaptive nervous system plasticity. 15…”

Section: Discussionmentioning

confidence: 99%

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report

Chapman,

Tupper,

Yousef

et al. 2023

A&A Practice

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A 67-year-old man presented with severe 9 of 10 intractable pain of the left shoulder joint after arthroplasty and revision surgeries, with associated weakness, atrophy, and limited range of motion in all directions. Dorsal root ganglion stimulation (DRG-S) at the left C4, C5, and C6 levels was used after failed conservative and interventional measures, resulting in significant improvement in pain, function, and quality of life measures through 6 months postimplantation. Larger studies should examine if DRG-S is effective in treating chronic arthritic joint pain as well as chronic postsurgical pain of the shoulder that is not predominantly neuropathic.

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Section: Discussionmentioning

confidence: 99%

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report

Chapman,

Tupper,

Yousef

et al. 2023

A&A Practice

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“…Particularly in the stages of OA, when inflammation is more pronounced, these anti-inflammatory effects may have therapeutic value [ 121 ]. This hypothesis is supported by the fact that upregulation of parasympathetic tone via vagal electrical stimulation is successfully used in RA therapy to induce local and systemic anti-inflammatory effects [ 222 ]. Currently, there is no curative treatment for OA, and therefore, there is an urgent need for novel causal therapy options.…”

Section: Sns As Therapeutic Target In Mild Chronic Inflammationmentioning

confidence: 99%

Role of the Sympathetic Nervous System in Mild Chronic Inflammatory Diseases: Focus on Osteoarthritis

Sohn¹,

Jenei-Lanzl²

2023

Neuroimmunomodulation

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The sympathetic nervous system (SNS) is a major regulatory mediator connecting the brain and the immune system that influences accordingly inflammatory processes within the entire body. In the periphery, the SNS exerts its effects mainly via its neurotransmitters norepinephrine (NE) and epinephrine (E), which are released by peripheral nerve endings in lymphatic organs and other tissues. Depending on their concentration, NE and E bind to specific α- and β-adrenergic receptor subtypes and can cause both pro- and anti-inflammatory cellular responses. The co-transmitter neuropeptide Y, adenosine triphosphate, or its metabolite adenosine are also mediators of the SNS. Local pro-inflammatory processes due to injury or pathogens lead to an activation of the SNS, which in turn induces several immunoregulatory mechanisms with either pro- or anti-inflammatory effects depending on neurotransmitter concentration or pathological context. In chronic inflammatory diseases, the activity of the SNS is persistently elevated and can trigger detrimental pathological processes. Recently, the sympathetic contribution to mild chronic inflammatory diseases like osteoarthritis (OA) has attracted growing interest. OA is a whole-joint disease and is characterized by mild chronic inflammation in the joint. In this narrative article, we summarize the underlying mechanisms behind the sympathetic influence on inflammation during OA pathogenesis. In addition, OA comorbidities also accompanied by mild chronic inflammation, such as hypertension, obesity, diabetes, and depression, will be reviewed. Finally, the potential of SNS-based therapeutic options for the treatment of OA will be discussed.

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“…Even though OA can affect any synovial joint, it occurs most often in the knee regarding larger joints [3]. In OA, progressive degeneration of articular cartilage, subchondral sclerosis and synovial inflammation form a vicious circle that manifests in chronic pain, reduced mobility and the onset of chronic comorbidities [4]. Pharmacological treatments for OA are mostly restricted to symptom relief and to date, there is no disease-modifying drug available counteracting OA progression [5].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a possible autonomic nervous system (ANS) dysfunction with a shift towards a more prominent Sohn et al Journal of Translational Medicine (2024) 22:467 sympathetic nervous system (SNS), gained prominence in OA research as an additional risk factor [4]. The ANS plays a critical role in joint homeostasis and is implicated in the pathogenesis of OA [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the ANS is a pivotal regulatory mediator between the brain and the immune system, with SNS activity having a particularly profound influence on inflammatory processes [9]. Thus, an altered autonomic balance could increase vulnerability to inflammatory stimuli or impair the ability to combat inflammatory pathologies, for example during OA [4].…”

Section: Introductionmentioning

confidence: 99%

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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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Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis

Cited by 7 publications

References 117 publications

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report

Role of the Sympathetic Nervous System in Mild Chronic Inflammatory Diseases: Focus on Osteoarthritis

Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance

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