Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain

Raoof, Ramin; Gil, Christian Martin; Lafeber, Floris P. J. G.; Visser, Harry; Prado, Judith; Versteeg, Sabine; Pascha, Mirte N.; Heinemans, A.; Adolfs, Youri; Pasterkamp, R. Jeroen; Wood, John N.; Mastbergen, S.C.; Eijkelkamp, Niels

doi:10.1523/jneurosci.1787-20.2021

Cited by 51 publications

(54 citation statements)

References 64 publications

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“…For example, macrophage accumulation in the dorsal root ganglia appears to mediate pain in mouse models of osteoarthritis. 14 These results suggest novel therapeutic strategies for KOA will require the modulation or prevention of inflammation which could be of value for postmenopausal patients.…”

Section: Inflammationmentioning

confidence: 98%

Knee osteoarthritis in midlife women: unique considerations and comprehensive management

2022

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Objective: Knee osteoarthritis (KOA) is a common musculoskeletal condition that particularly afflicts women in menopause. The purpose of this review is to describe the pathophysiology and treatment considerations for this subset of the population.Methods: Medline/PubMed indexed articles related to the pathophysiology, diagnosis, and management of osteoarthritis were included in this narrative review.Results and Conclusion: Menopause has a multitude of effects that affect KOA, including hormonal shifts; loss of bone mineral density, muscle mass, and tendon strength; and changes to pain perception. Here, we discuss how a practitioner can assess the factors that are known to worsen KOA symptoms, including postural (spine, pelvic, and knee) alignment and functional muscle strength. The development of an effective exercise program is at the forefront of management. Optimizing other lifestyle factors including nutrition and sleep are particularly important in this patient population. Sleep disturbance from vasomotor symptoms can also increase perception of knee pain, for which pharmacologic options such as gabapentin or duloxetine may be pursued. In total, these interventions have large ramifications in decreasing pain and increasing function through improved range of motion, body composition, and walking speed in women with KOA.

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Section: Inflammationmentioning

confidence: 98%

Knee osteoarthritis in midlife women: unique considerations and comprehensive management

2022

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“…The deletion of CCR2 was also shown to inhibit the DRG macrophage infiltration and reduce pain-related behaviors ( 166 , 167 ). Recently, Raoof et al ( 193 ) reported in rat models of OA (MIA and Groove surgery induced OA), that DRG macrophages display an M1-like proinflammatory phenotype, and systemic or local depletion of DRG macrophages reduce OA pain without affecting the pathology ( 193 ). Moreover, the inhibition of M1-like macrophages in DRG through intrathecal administration of an IL4-IL10 fusion protein or M2-like macrophages also reduced OA pain ( 193 ).…”

Section: The Neuroimmune Crosstalk In Joint Disordersmentioning

confidence: 99%

“…Tewari et al ( 190 ) showed that the conditioned medium from NGF-stimulated nociceptors modified macrophages gene transcription, upregulating the expression of inflammatory mediators and chemokines, such as IL-1β, IL6, and CCL22 ( 190 ). Moreover, it was shown, in an in vitro experiment, that sensory neurons that innervate the OA knee joint in the rat polarize DRG macrophages into an M1-like phenotype ( 193 ).…”

Section: The Neuroimmune Crosstalk In Joint Disordersmentioning

confidence: 99%

The Neuroimmune Interplay in Joint Pain: The Role of Macrophages

et al. 2022

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Chronic pain associated with joint disorders, such as rheumatoid arthritis (RA), osteoarthritis (OA) and implant aseptic loosening (AL), is a highly debilitating symptom that impacts mobility and quality of life in affected patients. The neuroimmune crosstalk has been demonstrated to play a critical role in the onset and establishment of chronic pain conditions. Immune cells release cytokines and immune mediators that can activate and sensitize nociceptors evoking pain, through interaction with receptors in the sensory nerve terminals. On the other hand, sensory and sympathetic nerve fibers release neurotransmitters that bind to their specific receptor expressed on surface of immune cells, initiating an immunomodulatory role. Macrophages have been shown to be key players in the neuroimmune crosstalk. Moreover, macrophages constitute the dominant immune cell population in RA, OA and AL. Importantly, the targeting of macrophages can result in anti-nociceptive effects in chronic pain conditions. Therefore, the aim of this review is to discuss the nature and impact of the interaction between the inflammatory response and nerve fibers in these joint disorders regarding the genesis and maintenance of pain. The role of macrophages is highlighted. The alteration in the joint innervation pattern and the inflammatory response are also described. Additionally, the immunomodulatory role of sensory and sympathetic neurotransmitters is revised.

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“…Evidence from preclinical and clinical studies has suggested that the presence of macrophages in the joints and DRGs, direct or indirectly contributes to the generation and maintenance of pain in OA (for a review, see ( Geraghty et al, 2021 )). In murine models of OA, macrophage depletion has been associated with reduction of OA symptoms, including osteophyte formation ( Blom et al, 2004 ) and pain ( Raoof et al, 2021 ). In a clinical study, activated macrophages found in 76% of OA knee, were associated with OA pain severity and radiographic OA severity ( Kraus et al, 2016 ).…”

Section: Sex Differences and Innate-immunity-related Oa Pain Mediatorsmentioning

confidence: 99%

“…Differences in macrophage phenotype also appears to contribute to the OA pathogenesis and studies in this direction have been conducted ( Wood et al, 2019 ; Chou et al, 2020 ), although further investigation is needed. In addition to the synovium and synovial fluid, DRG macrophages have also been described to contribute to both the initiation and persistence of OA pain ( Raoof et al, 2021 ). However, whether these mechanisms in which macrophages are involved in OA pain are different between men and women is unknown.…”

Section: Sex Differences and Innate-immunity-related Oa Pain Mediatorsmentioning

confidence: 99%

Innate Immunity at the Core of Sex Differences in Osteoarthritic Pain?

et al. 2022

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Osteoarthritis (OA) is a progressive whole-joint disease; no disease-modifying drugs are currently available to stop or slow its process. Symptoms alleviation is the only treatment option. OA is the major cause of chronic pain in adults, with pain being the main symptom driving patients to seek medical help. OA pathophysiology is closely associated with the innate immune system, which is also closely linked to pain mediators leading to joint pain. Pain research has shown sex differences in the biology of pain, including sexually dimorphic responses from key cell types in the innate immune system. Not only is OA more prevalent in women than in men, but women patients also show worse OA outcomes, partially due to experiencing more pain symptoms despite having similar levels of structural damage. The cause of sex differences in OA and OA pain is poorly understood. This review provides an overview of the involvement of innate immunity in OA pain in joints and in the dorsal root ganglion. We summarize the emerging evidence of sex differences regarding innate immunity in OA pain. Our main goal with this review was to provide a scientific foundation for future research leading to alternative pain relief therapies targeting innate immunity that consider sex differences. This will ultimately lead to a more effective treatment of pain in both women and men.

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Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain

Cited by 51 publications

References 64 publications

Knee osteoarthritis in midlife women: unique considerations and comprehensive management

Knee osteoarthritis in midlife women: unique considerations and comprehensive management

The Neuroimmune Interplay in Joint Pain: The Role of Macrophages

Innate Immunity at the Core of Sex Differences in Osteoarthritic Pain?

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