Transient receptor potential ankyrin 1 receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents.

Published on Nov 1, 2013in Arthritis & Rheumatism9.586
路 DOI :10.1002/ART.38112
Gabriela Trevisan28
Estimated H-index: 28
(UFSM: Universidade Federal de Santa Maria),
Carin Hoffmeister11
Estimated H-index: 11
(UFSM: Universidade Federal de Santa Maria)
+ 9 AuthorsJuliano Ferreira54
Estimated H-index: 54
(UFSC: Universidade Federal de Santa Catarina)
Objective Gout is a common cause of inflammatory arthritis and is provoked by the accumulation of monosodium urate (MSU) crystals. However, the underlying mechanisms of the pain associated with acute attacks of gout are poorly understood. The aim of this study was to evaluate the role of transient receptor potential ankyrin 1 (TRPA-1) and TRPA-1 stimulants, such as H2O2, in a rodent model of MSU-induced inflammation. Methods MSU or H2O2 was injected into the hind paws of rodents or applied in cultured sensory neurons, and the intracellular calcium response was measured in vitro. Inflammatory or nociceptive responses in vivo were evaluated using pharmacologic, genetic, or biochemical tools and methods. Results TRPA-1 antagonism, TRPA-1 gene deletion, or pretreatment of peptidergic TRP-expressing primary sensory neurons with capsaicin markedly decreased MSU-induced nociception and edema. In addition to these neurogenic effects, MSU increased H2O2 levels in the injected tissue, an effect that was abolished by the H2O2-detoxifying enzyme catalase. H2O2, but not MSU, directly stimulated sensory neurons through the activation of TRPA-1. The nociceptive responses evoked by MSU or H2O2 injection were attenuated by the reducing agent dithiothreitol. In addition, MSU injection increased the expression of TRPA-1 and TRP vanilloid channel 1 (TRPV-1) and also enhanced cellular infiltration and interleukin-1尾 levels, and these effects were blocked by TRPA-1 antagonism. Conclusion Our results suggest that MSU injection increases tissue H2O2, thereby stimulating TRPA-1 on sensory nerve endings to produce inflammation and nociception. TRPV-1, by a previously unknown mechanism, also contributes to these responses.
馃摉 Papers frequently viewed together
#1Kenneth L. Rock (UMMS: University of Massachusetts Medical School)H-Index: 96
#2Hiroshi Kataoka (UMMS: University of Massachusetts Medical School)H-Index: 16
Last. Jiann-Jyh Lai (UMMS: University of Massachusetts Medical School)H-Index: 12
view all 3 authors...
Uric acid not only triggers inflammation in gout in its crystallized form, monosodium urate, but is also associated with comorbidities of the disease. New insights into the role of uric acid as a danger signal for both adaptive and innate immune responses could help to explain the pathogenesis of gout and point to potential new avenues of therapy for this and other sterile inflammatory diseases.
#1Noriyuki Hatano (Aichi Gakuin University)H-Index: 15
#2Yuka Itoh (Aichi Gakuin University)H-Index: 15
Last. Katsuhiko Muraki (Aichi Gakuin University)H-Index: 39
view all 9 authors...
Abstract Transient receptor potential ankyrin repeat 1 (TRPA1) forms calcium (Ca2+)- and zinc (Zn2+)- permeable ion channels that sense noxious substances. Despite of biological and clinical importance of TRPA1, there is little knowledge of the mechanisms that lead to transcriptional regulation of TRPA1 and of the functional role of transcriptionally induced-TRPA1. Here we show induction of TRPA1 by inflammatory mediators and delineate the underlying molecular mechanisms and functional relevance...
#1Elizabeth S. Fernandes ('KCL': King's College London)H-Index: 30
#2M. A. Fernandes ('KCL': King's College London)H-Index: 2
Last. Julie Keeble ('KCL': King's College London)H-Index: 21
view all 3 authors...
The transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) channels are members of the TRP superfamily of structurally related, non-selective cation channels. It is rapidly becoming clear that the functions of TRPV1 and TRPA1 interlink with each other to a considerable extent. This is especially clear in relation to pain and neurogenic inflammation where TRPV1 is coexpressed on the vast majority of TRPA1-expressing sensory nerves and both integrate a variety of no...
#1Edin茅ia L. Andrade (UFSC: Universidade Federal de Santa Catarina)H-Index: 15
#2Flavia Carla Meotti (USP: University of S茫o Paulo)H-Index: 28
Last. Jo茫o B. Calixto (UFSC: Universidade Federal de Santa Catarina)H-Index: 93
view all 3 authors...
Abstract The necessity of safe and effective treatments for chronic pain has intensified the search for new analgesic drugs. In the last few years, members of a closely-related family of ion channels, called transient receptor potential (TRP) have been identified in different cell types and their functions in physiological and pathological conditions have been characterized. The transient receptor potential ankyrin 1 (TRPA1), originally called ANKTM1 (ankyrin-like with transmembrane domains prot...
#1Stephen E. Malawista (Yale University)H-Index: 68
Last. Paul H. Naccache (Laval University)H-Index: 58
view all 3 authors...
This is a discussion of acute gouty arthritis, seen for over 50 years of engagement. It addresses the evolution of our current understanding of the interaction between urate crystals and key cellular components of the gouty inflammatory paroxysm, with new material on pathogenesis.
#1Magdalene M. MoranH-Index: 2
#2Michael Allen McAlexander (GSK: GlaxoSmithKline)H-Index: 4
Last. Arpad Szallasi (Drexel University)H-Index: 56
view all 4 authors...
Transient receptor potential (TRP) channels are a diverse family of cation channels. Here, the authors discuss recent developments in this area, highlight recent developments and setbacks in the field of pain research and analyse TRP channels as targets for skin, pulmonary and urological disorders.
#1Carin Hoffmeister (UFSM: Universidade Federal de Santa Maria)H-Index: 11
#2Gabriela Trevisan (UFSM: Universidade Federal de Santa Maria)H-Index: 28
Last. Juliano FerreiraH-Index: 54
view all 6 authors...
Abstract Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (ED 50 [ie, the necessary dose of MSU to elicit 50% of the response relative to the control value]聽=聽0.04 [95% confidence interval 0.01鈥0.11]聽mg/paw) and edema (ED 50 =聽0.08 [95% confidence interval 0.04鈥...
#1Romina Nassini (UniFI: University of Florence)H-Index: 36
#2Maarten Gees (Katholieke Universiteit Leuven)H-Index: 11
Last. Pierangelo Geppetti (UniFI: University of Florence)H-Index: 99
view all 15 authors...
Platinum-based anticancer drugs cause neurotoxicity. In particular, oxaliplatin produces early-developing, painful, and cold-exacerbated paresthesias. However, the mechanism underlying these bothersome and dose-limiting adverse effects is unknown. We hypothesized that the transient receptor potential ankyrin 1 (TRPA1), a cation channel activated by oxidative stress and cold temperature, contributes to mechanical and cold hypersensitivity caused by oxaliplatin and cisplatin. Oxaliplatin and cispl...
#1Bernd Nilius (Katholieke Universiteit Leuven)H-Index: 129
#2Jean Prenen (Katholieke Universiteit Leuven)H-Index: 57
Last. Grzegorz Owsianik (Katholieke Universiteit Leuven)H-Index: 41
view all 3 authors...
Transient receptor potential (TRP) channels have been extensively studied over the past years. Yet, in most cases, the gating mechanisms of these polymodal cation channels still remain a puzzle. Using the nociceptive channel TRPA1 as an example, we discuss the role of dynamic regulation of the pore size (pore dilatation) on channel gating. Additionally, we critically revise current knowledge of the role of intracellular domains, such as ankyrin repeats and EF hand motifs, in channel activation a...
#1Erica S. Schwartz (University of Pittsburgh)H-Index: 17
#2Julie A. Christianson (University of Pittsburgh)H-Index: 24
Last. Gerald F. Gebhart (University of Pittsburgh)H-Index: 99
view all 7 authors...
Background & Aims The transient receptor potential (TRP) channels TRPV1 and TRPA1 have each been associated with regulation of efferent properties of primary afferent neurons that initiate neurogenic inflammation and are required for the development of inflammatory hyperalgesia. To evaluate the role of these channels in producing pain during pancreatic inflammation, we studied pancreatic nodose ganglion (NG) and dorsal root ganglion (DRG) sensory neurons (identified by content of retrograde trac...
Cited By54
Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs)....
#1Diulle Spat Peres (UFSM: Universidade Federal de Santa Maria)H-Index: 2
#2Maria Carolina Theisen (UFSM: Universidade Federal de Santa Maria)H-Index: 2
Last. Tuane Bazanella Sampaio (UFSM: Universidade Federal de Santa Maria)H-Index: 12
view all 17 authors...
Abstract null null Progressive multiple sclerosis (PMS) is a neurological disease associated with the development of depression and anxiety, but treatments available are unsatisfactory. The transient receptor potential ankyrin 1 (TRPA1) is a cationic channel activated by reactive compounds, and the blockage of this receptor can reduce depression- and anxiety-like behaviors in naive mice. Thus, we investigated the role of TRPA1 in depression- and anxiety-like behaviors in a PMS model in mice. PMS...
#1Ruixiang Chen (ZJNU: Zhejiang Chinese Medical University)H-Index: 5
#2Chengyu Yin (ZJNU: Zhejiang Chinese Medical University)H-Index: 8
Last. Boyi Liu (ZJNU: Zhejiang Chinese Medical University)H-Index: 19
view all 4 authors...
Chronic pain affects the life quality of the suffering patients and posts heavy problems to the health care system. Conventional medications are usually insufficient for chronic pain management and oftentimes results in many adverse effects. The NLRP3 inflammasome controls the processing of proinflammatory cytokine interleukin 1尾 (IL-1尾) and is implicated in a variety of disease conditions. Recently, growing number of evidence suggests that NLRP3 inflammasome is dysregulated under chronic pain c...
#1Qiang鈥恮ei Liu (Chinese PLA General Hospital)
#2Long Feng (Chinese PLA General Hospital)H-Index: 1
Last. Longhe Xu (Chinese PLA General Hospital)H-Index: 1
view all 6 authors...
Abstract Background: Bone cancer pain (BCP) significantly affects patient quality of life, results in great bodily and emotional pain, and creates difficulties in follow-up treatment and normal life. Transient receptor potential ankyrin 1 (TRPA1) is an essential transduction ion channel related to neuropathic and inflammatory pain. However, the role of TRPA1 in BCP remains poorly understood. This study aimed to explore the relationship between TRPA1 and BCP. Methods: A BCP model was induced by W...
Transient receptor potential ankyrin 1 (TRPA1) is a membrane-bound ion channel found in neurons, where it mediates nociception and neurogenic inflammation. Recently, we have discovered that TRPA1 is also expressed in human osteoarthritic (OA) chondrocytes and downregulated by the anti-inflammatory drugs aurothiomalate and dexamethasone. We have also shown TRPA1 to mediate inflammation, pain, and cartilage degeneration in experimental osteoarthritis. In this study, we investigated the role of TRP...
#1Chengyu YinH-Index: 8
#2Boyu LiuH-Index: 9
Last. Boyi LiuH-Index: 19
view all 15 authors...
Objective: Gout, induced by monosodium urate (MSU) crystal deposition in joint tissues, provokes severe pain and impacts life quality of patients. However, the mechanisms underlying gout pain are still incompletely understood. Methods: We established a mouse gout model by intra-articularly injection of MSU crystals into the ankle joint of wild type and genetic knockout mice. RNA-Sequencing, in vivo molecular imaging, Ca2+ imaging, reactive oxygen species (ROS) generation, neutrophil influx and n...
#1Gabriele Cheiran Pereira (UFSM: Universidade Federal de Santa Maria)H-Index: 4
#2Elisa Piton (UFSM: Universidade Federal de Santa Maria)H-Index: 1
Last. Guilherme Vargas Bochi (UFSM: Universidade Federal de Santa Maria)H-Index: 18
view all 12 authors...
Abstract Depression is one of the most common mood disorders, which affects one in six people at some point in life. However, the treatment of this disease is still a challenge. Chronic corticosterone administration (CCA) is a widely used animal model to study the mechanisms involved, as well as possible therapeutic strategies for the treatment of depression. Moreover, elevated oxidative stress has been observed in psychiatric disorders, including major depression and, in this context, antioxida...
#1Piyush Jain (UniFI: University of Florence)H-Index: 2
#2Serena Materazzi (UniFI: University of Florence)H-Index: 36
Last. Romina Nassini (UniFI: University of Florence)H-Index: 36
view all 11 authors...
Pain evoked by visceral inflammation is often 鈥榬eferred鈥 to the somatic level. Transient receptor potential ankyrin 1 (TRPA1) has been reported to contribute to visceral pain-like behavior in dextran sulfate sodium (DSS)-evoked colitis. However, the role of TRPA1 in somatic component of hypersensitivity due to visceral inflammation is unknown. The present study investigated the role of TRPA1 in colitis-evoked mechanical hypersensitivity at the somatic level. Colitis was induced in mice by adding...
#1Indiara Brusco (UFSM: Universidade Federal de Santa Maria)H-Index: 11
#2Simone Li Puma (UniFI: University of Florence)H-Index: 9
Last. Gabriela Trevisan (UFSM: Universidade Federal de Santa Maria)H-Index: 28
view all 15 authors...
: Antineoplastic therapy has been associated with pain syndrome development characterized by acute and chronic pain. The chemotherapeutic agent dacarbazine, used mainly to treat metastatic melanoma, is reported to cause painful symptoms, compromising patient quality of life. Evidence has proposed that transient receptor potential ankyrin 1 (TRPA1) plays a critical role in chemotherapy-induced pain syndrome. Here, we investigated whether dacarbazine causes painful hypersensitivity in naive or mel...
#1Chengyu Yin (ZJNU: Zhejiang Chinese Medical University)H-Index: 8
#2Boyu Liu (ZJNU: Zhejiang Chinese Medical University)H-Index: 9
Last. Boyi Liu (ZJNU: Zhejiang Chinese Medical University)H-Index: 19
view all 9 authors...
BACKGROUND AND PURPOSE: Gout arthritis, which is provoked by monosodium urate (MSU) crystal accumulation in the joint and periarticular tissues, induces severe pain and affects quality of life of the patients. Eucalyptol (1,8-cineol), the principal component in the essential oils of eucalyptus leaves, is known to possess anti-inflammatory and analgesic properties. We aimed to examine the therapeutic effects of eucalyptol on gout arthritis and related mechanisms. EXPERIMENTAL APPROACH: A mouse mo...
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.