Dataset Information

Osteoarthritis Pain.

ABSTRACT: Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C-C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/β-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.

SUBMITTER: Yu H

PROVIDER: S-EPMC9105801 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Osteoarthritis Pain.

Yu Huan H Huang Tianwen T Lu William Weijia WW Tong Liping L Chen Di D

International journal of molecular sciences 20220422 9

Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These ...[more]

PMID: 35563035

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Project description:ObjectiveTo examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations.ResultsThere were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant ± intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain.ConclusionKnee pain patterns appear to be related to peripheral ± central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

Project description:Pain is the major debilitating symptom of osteoarthritis (OA), which is difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute to OA pain. Immune cells regulate the sensory system, but little is known about the involvement of immune cells in OA pain. Here, we report that macrophages accumulate in the dorsal root ganglia (DRG) distant from the site of injury in two rodent models of OA. DRG macrophages acquired an M1-like phenotype, and depletion of DRG macrophages resolved OA pain in male and female mice. Sensory neurons innervating the damaged knee joint shape DRG macrophages into an M1-like phenotype. Persisting OA pain, accumulation of DRG macrophages, and programming of DRG macrophages into an M1-like phenotype were independent of Nav1.8 nociceptors. Inhibition of M1-like macrophages in the DRG by intrathecal injection of an IL4-IL10 fusion protein or M2-like macrophages resolved persistent OA pain. In conclusion, these findings reveal a crucial role for macrophages in maintaining OA pain independent of the joint damage and suggest a new direction to treat OA pain.SIGNIFICANCE STATEMENT In OA patients pain poorly correlates with joint tissue changes indicating mechanisms other than only tissue damage that cause pain in OA. We identified that DRG containing the somata of sensory neurons innervating the damaged knee are infiltrated with macrophages that are shaped into an M1-like phenotype by sensory neurons. We show that these DRG macrophages actively maintain OA pain remotely and independent of joint damage. The phenotype of these macrophages is crucial for a pain-promoting role. Targeting the phenotype of DRG macrophages with either M2-like macrophages or a cytokine fusion protein that skews macrophages into an M2-like phenotype resolves OA pain. Our work reveals a mechanism that contributes to the maintenance of OA pain distant from the affected knee joint and suggests that dorsal root ganglia macrophages are a target to treat osteoarthritis chronic pain.

Dataset Information

Osteoarthritis Pain.

Publications

Osteoarthritis Pain.

Similar Datasets

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