Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain: associations with pain severity and central sensitization

Bjurström, Martin F.; Blennow, Kaj; Zetterberg, Henrik; Bodelsson, Mikael; Waldén, Markus; Dietz, Nicholas; Hall, Sara; Hansson, Oskar; Irwin, Michael R.; Mattsson‐Carlgren, Niklas

doi:10.1097/pr9.0000000000000988

Cited by 11 publications

(9 citation statements)

References 52 publications

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“…Moreover, the recent literature reported changes in cerebrospinal fluid composition that may be helpful in characterizing knee OA patients with pain sensitization, but the evaluation of these issues was besides the focus of this meta-analysis that was focused on altered pain perception. 18 Finally, in the meta-analysis comparing PPT of affected patients and healthy controls, the use of healthy controls without knee OA or pain as comparators does not allow for clear understanding of whether structural pathology versus pain symptomatology (or both) are relevant for the development of pain sensitization.…”

Section: Discussionmentioning

confidence: 99%

“… 15 The involvement of the nervous system with changes in nervous transmission and cerebrospinal fluid composition affecting level and characteristics of perceived pain leads to the use of the term “neuropathic pain,” to distinguish it from “nociceptive pain” historically considered related to knee OA. 16 - 18 As “neuropathic” pain is a broader concept pertaining different pathologic conditions outside the OA field 19 (i.e., neuropathies, central poststroke pain, etc.) and entailing the presence of a demonstrable neurologic lesion, the term “nociplastic pain” has been introduced to account for the possible involvement of the nervous system in musculoskeletal diseases.…”

Section: Introductionmentioning

confidence: 99%

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High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression

Previtali¹,

Capone²,

Marchettini

et al. 2022

CARTILAGE

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Objective The aim of this meta-analysis was to study the evidence on pain sensitization in knee osteoarthritis (OA), providing a quantitative synthesis of its prevalence and impact. Factors associated with pain sensitization were also investigated. Methods Meta-analysis; PubMed (MEDLINE), Cochrane Central Register (CENTRAL), and Web of Science were searched on February 2021. Level I to level IV studies evaluating the presence of pain sensitization in patients with symptomatic knee OA, documented through a validated method (questionnaires or quantitative sensory testing), were included. The primary outcome was the prevalence of pain sensitization. Factors influencing the prevalence were also evaluated, as well as differences in terms of pain thresholds between knee OA patients and healthy controls. Results Fifty-three articles including 7,117 patients were included. The meta-analysis of proportion documented a prevalence of pain sensitization of 20% (95% confidence interval [CI] = 16%-26%) with a significant heterogeneity of results ( I2 = 89%, P < 0.001). The diagnostic tool used was the main factor influencing the documented prevalence of pain sensitization ( P = 0.01). Knee OA patients presented higher pain sensitivity compared with healthy controls, both in terms of local pressure pain threshold (standardized mean difference [SMD] = −1.00, 95% CI = −1.67 to −0.32, P = 0.007) and distant pressure pain threshold (SMD = −0.54, 95% CI = −0.76 to −0.31, P < 0.001). Conclusions Knee OA pain presents features that are consistent with a significant degree of pain sensitization. There is a high heterogeneity in the reported results, mainly based on the diagnostic tool used. The identification of the best methods to detect pain sensitization is warranted to correctly evaluate and manage symptoms of patients affected by knee OA. Registration: PROSPERO CRD42019123347.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression

Previtali¹,

Capone²,

Marchettini

et al. 2022

CARTILAGE

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“…In contrast to fast pain, the persistent inflammatory microenvironment in the OA joint causes peripheral and central nerve sensitization with typical features of mechanical allodynia and hyperalgesia around the joint. 97 , 98 Despite the unclear mechanism of nerve sensitization, joint replacement can reverse this paresthesia, suggesting that the central nervous system is highly plastic and that peripheral stimulation may be a major intrinsic factor driving central nerve sensitization. 99 A better understanding of the mechanisms of OA-associated pain will help in the diagnosis and treatment of OA.…”

Section: Osteoarthritis-associated Painmentioning

confidence: 99%

Current understanding of osteoarthritis pathogenesis and relevant new approaches

et al. 2022

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Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development. To better understand the pathological mechanisms of OA, new approaches, methods, and techniques need to be used to understand OA pathogenesis. In this review, we first focus on the epigenetic regulation of OA, with a particular focus on DNA methylation, histone modification, and microRNA regulation, followed by a summary of several key mediators in OA-associated pain. We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain, such as CRISPR, scRNA sequencing, and lineage tracing. Next, we discuss the timely updates concerning cell death regulation in OA pathology, including pyroptosis, ferroptosis, and autophagy, as well as their individual roles in OA and potential molecular targets in treating OA. Finally, our review highlights new directions on the role of the synovial lymphatic system in OA. An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

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“…A variety of persistent pain conditions can be effectively treated with analgesia using drugs that target and improve these monoaminergic systems, such as amitriptyline and serotonin noradrenaline reuptake inhibitors. A higher level of serotonin and dopamine metabolites in the cerebrospinal fluid of OA patients with disabling pain has been associated with increased pain severity and CS [ 63 ]. The evidence provided here underlines the fact that CNS monoaminergic activity plays a significant role in the pain processes associated with OA.…”

Section: Reviewmentioning

confidence: 99%

Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain

Ohashi¹,

Uchida²,

Fukushima³

et al. 2023

Cureus

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Pain, the primary symptom of osteoarthritis (OA), reduces both the quality and quantity of life for patients. The pathophysiology of OA pain is complex and often difficult to explain solely by radiological structural changes. One reason for this discrepancy is pain sensitization (peripheral sensitization [PS] and central sensitization [CS]) in OA. Thus, an understanding of pain sensitization is important when considering treatment strategies and development for OA pain. In recent years, pro-inflammatory cytokines, nerve growth factors (NGFs), and serotonin have been identified as causative agents that induce peripheral and central sensitization and are becoming therapeutic targets for OA pain. However, the characteristics of the clinical manifestations of pain sensitization elicited by these molecules remain unclear, and it is not well understood who among OA patients should receive the therapeutic intervention. Thus, this review summarizes evidence on the pathophysiology of peripheral and central sensitization in OA pain and the clinical features and treatment options for this condition. While the majority of the literature supports the existence of pain sensitization in chronic OA pain, clinical identification and treatment of pain sensitization in OA are still in their infancy, and future studies with good methodological quality are needed.

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Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain: associations with pain severity and central sensitization

Abstract: In patients with osteoarthritis undergoing total hip arthroplasty, higher cerebrospinal fluid concentrations of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization.

Cited by 11 publications

References 52 publications

High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression

High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression

Current understanding of osteoarthritis pathogenesis and relevant new approaches

Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain

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