Role of TrkA signalling and mast cells in the initiation of osteoarthritis pain in the monoiodoacetate model

Valente, João de Sousa; Calvo, Laura; Vacca, Valentina; Simeoli, Raffaele; Arévalo, Juan Carlos; Malcangio, Marzia

doi:10.1016/j.joca.2017.08.006

Cited by 51 publications

(47 citation statements)

References 31 publications

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“…In the presence of overt joint swelling and allodynia on day 5 after serum transfer, we observed increased DRG levels of PGD 2 , which is pronociceptive. 28 However, by day 25, where allodynia is present in the absence of joint swelling, PGD 2 levels were no longer heightened in K/BxN DRG, and we observed lower levels of MaR1, which is a proresolution LM. 23 Therefore, our analysis indicates distinct lipid profiles in DRG at day 5 (peak joint swelling) and day 25 (postjoint swelling) demonstrating that alternate mechanisms may be in place further away from the joint leading to maintained pain in RA dissociated from joint swelling.…”

Section: Discussionmentioning

confidence: 47%

Imbalance of proresolving lipid mediators in persistent allodynia dissociated from signs of clinical arthritis

Allen

Montague-Cardoso

Simeoli

et al. 2020

Pain

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Rheumatoid arthritis-associated pain is poorly managed, often persisting when joint inflammation is pharmacologically controlled. Comparably, in the mouse K/BxN serum-transfer model of inflammatory arthritis, hind paw nociceptive hypersensitivity occurs with ankle joint swelling (5 days after immunisation) persisting after swelling has resolved (25 days after immunisation). In this study, lipid mediator (LM) profiling of lumbar dorsal root ganglia (DRG), the site of sensory neuron cell bodies innervating the ankle joints, 5 days and 25 days after serum transfer demonstrated a shift in specialised proresolving LM profiles. Persistent nociception without joint swelling was associated with low concentrations of the specialised proresolving LM Maresin 1 (MaR1) and high macrophage numbers in DRG. MaR1 application to cultured DRG neurons inhibited both capsaicin-induced increase of intracellular calcium ions and release of calcitonin gene-related peptide in a dose-dependent manner. Furthermore, in peritoneal macrophages challenged with lipopolysaccharide, MaR1 reduced proinflammatory cytokine expression. Systemic MaR1 administration caused sustained reversal of nociceptive hypersensitivity and reduced inflammatory macrophage numbers in DRG. Unlike gabapentin, which was used as positive control, systemic MaR1 did not display acute antihyperalgesic action. Therefore, these data suggest that MaR1 effects observed after K/BxN serum transfer relate to modulation of macrophage recruitment, more likely than to direct actions on sensory neurons. Our study highlights that, in DRG, aberrant proresolution mechanisms play a key role in arthritis joint pain dissociated from joint swelling, opening novel approaches for rheumatoid arthritis pain treatment.

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Section: Discussionmentioning

confidence: 47%

Imbalance of proresolving lipid mediators in persistent allodynia dissociated from signs of clinical arthritis

Allen

Montague-Cardoso

Simeoli

et al. 2020

Pain

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“…Mast cells have roles in a variety of pathological conditions including chemotherapy‐induced neuropathic pain, osteoarthritis, and pelvic pain . We will review recent research suggesting that mast cells are important to the pathobiology of pain and pruritus in mast cell activation disease (MCAD), SCD, and cancer and in atopic dermatitis and psoriasis, respectively.…”

Section: Mast Cell's Contribution To the Pathobiology Of Pain And Prumentioning

confidence: 99%

Mast cell‐neural interactions contribute to pain and itch

Gupta

Harvima

2018

Immunological Reviews

217

189

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Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer.

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“…[104] Increased TrkA receptor signaling in MIA-induced OA in transgenic mice harboring a TrkA gain-of-function mutation resulted in increased pain accompanied by higher numbers of leukocytes, macrophages, and mast cells in the synovial fluid. [105] Interestingly, a close anatomical connection was observed between CD117+ mast cells and peptidergic C- fibers in the synovium, suggesting a role for cell-to-nociceptor communication in OA pain. [105] In human OA synovium, prevalence of mast cells is relatively high, but not associated with self-reported knee pain.…”

Section: Peripheral Mechanisms Of Oa Painmentioning

confidence: 99%

“…[105] Interestingly, a close anatomical connection was observed between CD117+ mast cells and peptidergic C- fibers in the synovium, suggesting a role for cell-to-nociceptor communication in OA pain. [105] In human OA synovium, prevalence of mast cells is relatively high, but not associated with self-reported knee pain. [106] However, measures of sensitization were not included in this study and further research is necessary to examine the role of these cells in clinical OA.…”

Section: Peripheral Mechanisms Of Oa Painmentioning

confidence: 99%

Peripheral Mechanisms Contributing to Osteoarthritis Pain

et al. 2018

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Both peripheral and central mechanisms contribute to OA pain. Clinical evidence suggests that a strong peripheral nociceptive drive from the affected joint maintains pain and central sensitization associated with OA. Mediators present in the OA joint, including nerve growth factor, chemokines, cytokines, and inflammatory cells can contribute to sensitization. Furthermore, structural alterations in joint innervation and nerve damage occur in the course of OA. Several interrelated pathological processes, including joint damage, structural reorganization of joint afferents, low-grade inflammation, neuroplasticity, and nerve damage all contribute to the pain observed in OA. It can be anticipated that elucidating exactly how these mechanisms are operational in the course of progressive OA may lead to the identification of novel targets for intervention.

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Role of TrkA signalling and mast cells in the initiation of osteoarthritis pain in the monoiodoacetate model

Cited by 51 publications

References 31 publications

Imbalance of proresolving lipid mediators in persistent allodynia dissociated from signs of clinical arthritis

Imbalance of proresolving lipid mediators in persistent allodynia dissociated from signs of clinical arthritis

Mast cell‐neural interactions contribute to pain and itch

Peripheral Mechanisms Contributing to Osteoarthritis Pain

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