Involvement of Mast Cells in the Pathophysiology of Pain

Mai, Lijia; Liu, Qing; Huang, Fang; He, Hongwen; Fan, Wenguo

doi:10.3389/fncel.2021.665066

Cited by 21 publications

(20 citation statements)

References 116 publications

(144 reference statements)

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“…Mast cell-nerve cell spatial contacts has been verified both in vitro and in vivo [ 71 ]. The functional associations between mast cells and nerves have been proven at both the anatomic and the molecular levels [ 72 , 73 , 74 ]. The interaction between nerve cells and mast cells is mutual.…”

Section: Mast Cells and Acupuncture Analgesiamentioning

confidence: 99%

Mast Cells and Acupuncture Analgesia

Liu

et al. 2022

Cells

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Mast cells are widely distributed in various parts of the human body and play a vital role in the progression of many diseases. Recently, the close relationship between mast cells and acupoints was elucidated, and the role of mast cells in acupuncture analgesia has attracted the attention of researchers worldwide. Using mast cells, acupuncture analgesia and acupoint as key words to search CNKI, PubMed, Web of Science and other databases, combining the representative articles in these databases with the published research papers of our group, we summarized: The enrichment of mast cells and the dense arrangement of collagen fibers, microvessels, and nerves form the basis for acupoints as the reaction sites of acupuncture; acupuncture can cause the deformation of collagen fibers and activate TRPV channels on mast cells membrane, so as to stimulate mast cells to release bioactive substances and activate nerve receptors to generate analgesic effect; system biology models are set up to explain the quantitative process of information initiation and transmission at acupuncture points, and indicate that the acupuncture effect depends on the local mast cells density. In a conclusion, this review will give a scientific explanation of acupuncture analgesia from the material basis of acupoints, the local initiation, and afferent biological mechanism.

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Section: Mast Cells and Acupuncture Analgesiamentioning

confidence: 99%

Mast Cells and Acupuncture Analgesia

Liu

et al. 2022

Cells

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“…A substantial body of evidence, based on both animal and human studies, demonstrates that MC-derived NGF plays a pivotal role in the development of hypersensitivity during inflammation. 16,48,49 Therefore, it is no surprise that we found a significant increase in NGF concentration in the vulvar tissue after 24 hours of zymosan administration in the 1st and the 2nd round compared to the saline group. More critically, pretreatment with MCs stabilizer KF prevented the upregulation of NGF concentration in the vulva 24 hours after the zymosan administration in the 1st and the 2nd challenge.…”

mentioning

confidence: 59%

Characterization of Early Inflammatory Events Leading to Provoked Vulvodynia Development in Rats

Awad-Igbaria¹,

Dadon²,

Shamir³

et al. 2022

JIR

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Background: Provoked vulvodynia (PV) is the main cause of vulvar pain and dyspareunia. The etiology of PV has not yet been elucidated. However, PV is associated with a history of recurrent inflammation, and its often accompanied by increases in the numbers of mast cells (MCs) and sensory hyperinnervation in the vulva. Therefore, this study aimed to examine the role of MCs and the early inflammatory events in the development of chronic vulvar pain in a rat model of PV. Methods: Mechanical and thermal vulvar sensitivity was measured for 5 months following zymosan vulvar challenges. Vulvar changes in glutamate and nerve growth factor (NGF) were analyzed using ELISA. Immunofluorescence (IF) staining of the vulvar section after 20, 81, and 160 days of the zymosan challenge were performed to test MCs accumulation, hyperinnervation, and expression of pain channels (transient receptor potential vanilloid/ankyrin-1-TRPV1 & TRPA1) in vulvar neurons. Changes in the development of vulvar pain were evaluated following the administration of the MCs stabilizer ketotifen fumarate (KF) during zymosan vulvar challenges. Results: Zymosan-challenged rats developed significant mechanical and thermal vulvar sensitivity that persisted for over 160 days after the zymosan challenge. During inflammation, increased local concentrations of NGF and glutamate and a robust increase in MCs degranulation were observed in zymosan-challenged rats. In addition, zymosan-challenged rats displayed sensory hyperinnervation and an increase in the expression of TRPV1 and TRPA1. Treatment with KF attenuated the upregulated level of NGF during inflammation, modulated the neuronal modifications, reduced MCs accumulation, and enhanced mechanical hypersensitivity after repeated inflammation challenges. Conclusion:The present findings suggest that vulvar hypersensitivity is mediated by MCs accumulation, nerve growth, and neuromodulation of TRPV1 and TRPA1. Hence, KF treatment during the critical period of inflammation contributes to preventing chronic vulvar pain development.

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“…In an animal model of CP/CPPS called experimental autoimmune prostatitis (EAP), we have shown the importance of the activation of mast cells and its released tryptases acting on its receptor PAR2 in mediating pain in NOD/ShiLtJ mice. Research in the field of tryptase mediated pain has mostly focused on α/β-tryptases ( 6 ), and little attention has been given to the role played by the δ-tryptase isoform, a truncated protein and a supposedly catalytically inactive form ( 23 , 24 ). Intriguingly, in this study, we observed an elevated level of δ-tryptase in the EPS of patients with CP/CPPS.…”

Section: Discussionmentioning

confidence: 99%

“…Mast cells are a multifaceted and multifunctional immune cell that upon activation releases a plethora of pro-inflammatory mediators such as cytokines and chemokines as well as pain mediators including histamine, proteases (e.g., tryptases), serotonins, neurotrophins, neurotransmitters, and prostaglandin E2 (4)(5)(6)(7)(8)(9)(10). Mast cells also contain preformed pockets of immune mediators and neurotrophins, such as histamine and nerve growth factor (NGF) that can be rapidly released upon activation (11,12).…”

Section: Introductionmentioning

confidence: 99%

mMCP7, a Mouse Ortholog of δ Tryptase, Mediates Pelvic Tactile Allodynia in a Model of Chronic Pelvic Pain

Pattabiraman¹,

Liu²,

Paul³

et al. 2022

Front. Pain Res.

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Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a condition that affects a large number of men and has unknown etiology. We have previously demonstrated the presence of elevated levels of mast cell tryptase in expressed prostatic secretions (EPS) of CP/CPPS patients. In a murine model of CP/CPPS, we showed tryptase and its cognate receptor PAR2 as critical to the development of pelvic pain and lower urinary tract symptoms. Here, we extend these observations to demonstrate that an isoform of tryptase called delta (δ)-tryptase, is elevated in the EPS of patients with CP/CPPS and is correlated with pelvic pain symptoms. Using an Escherichia coli (CP1) -induced murine model of CP/CPPS, we demonstrated a differential response in C57BL/6J and NOD/ShiLtJ mice, with C57BL6/J mice being resistant to an increase in pelvic tactile allodynia, despite having equivalent levels of activated mast cells in the prostate. Activated tryptase+ve mast cells were observed to be in closer apposition to PGP9.5+ve nerve fibers in the prostate stroma of NOD/ShiLtJ in comparison to C57BL/6J mice. The mouse ortholog of δ-tryptase, mouse mast cell protease 7 (mMCP7) has been reported to be unexpressed in C57BL/6J mice. We confirmed the absence of mMCP7 in the prostates of C57BL/6J and its presence in NOD/ShiLtJ mice. To evaluate a role for mMCP7 in the differential allodynia responses, we performed direct intra-urethral instillations of mMCP7 and the beta (β)-tryptase isoform ortholog, mMCP6 in the CP1-infection model. mMCP7, but not mMCP6 was able to induce an acute pelvic allodynia response in C57BL/6J mice. In-vitro studies with mMCP7 on cultured mast cells as well as dissociated primary neurons demonstrated the ability to induce differential activation of pain and inflammation associated molecules compared to mMCP6. We conclude that mMCP7, and possibility its human ortholog δ-tryptase, may play an important role in mediating the development of pelvic tactile allodynia in the mouse model of pelvic pain and in patients with CP/CPPS.

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Involvement of Mast Cells in the Pathophysiology of Pain

Cited by 21 publications

References 116 publications

Mast Cells and Acupuncture Analgesia

Mast Cells and Acupuncture Analgesia

Characterization of Early Inflammatory Events Leading to Provoked Vulvodynia Development in Rats

mMCP7, a Mouse Ortholog of δ Tryptase, Mediates Pelvic Tactile Allodynia in a Model of Chronic Pelvic Pain

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