+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice--potential role for transient receptor potential ankyrin 1 in gout



Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice--potential role for transient receptor potential ankyrin 1 in gout



Plos One 10(2): E0117770



In gout, monosodium urate (MSU) crystals deposit intra-articularly and cause painful arthritis. In the present study we tested the hypothesis that Transient Receptor Poten-tial Ankyrin 1 (TRPA1), an ion channel mediating nociceptive signals and neurogenic in-flammation, is involved in MSU crystal-induced responses in gout by utilizing three experi-mental murine models. The effects of selective pharmacological inhibition (by HC-030031) and genetic depletion of TRPA1 were studied in MSU crystal-induced inflammation and pain by using 1) spontaneous weight-bearing test to assess MSU crystal-induced joint pain, 2) subcutaneous air-pouch model resembling joint inflammation to measure MSU crystal-induced cytokine production and inflammatory cell accumulation, and 3) MSU crystal-induced paw edema to assess acute vascular inflammatory responses and swelling. Intra-articularly injected MSU crystals provoked spontaneous weight shift off from the affected limb in wild type but not in TRPA1 knock-out mice referring alleviated joint pain in TRPA1 deficient animals. MSU crystal-induced inflammatory cell infiltration and accumulation of cytokines MCP-1, IL-6, IL-1beta, MPO, MIP-1alpha and MIP-2 into subcu-taneous air-pouch (resembling joint cavity) was attenuated in TRPA1 deficient mice and in mice treated with the selective TRPA1 inhibitor HC-030031 as compared to control animals. Further, HC-030031 treated and TRPA1 deficient mice developed tempered inflammatory edema when MSU crystals were injected into the paw. TRPA1 mediates MSU crystal-induced inflammation and pain in experimental models supporting the role of TRPA1 as a potential mediator and a drug target in gout flare.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059208582

Download citation: RISBibTeXText

PMID: 25658427

DOI: 10.1371/journal.pone.0117770


Related references

Transient receptor potential ankyrin 1 receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents. Arthritis and Rheumatism 65(11): 2984-2995, 2014

Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 contribute to the progression of colonic inflammation in dextran sulfate sodium-induced colitis in mice: Links to calcitonin gene-related peptide and substance P. Journal of Pharmacological Sciences 136(3): 121-132, 2018

Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropathic pain. Neuroscience 193: 440-451, 2012

A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis. Arthritis and Rheumatism 63(3): 819-829, 2013

Potential Role of Transient Receptor Potential Ankyrin 1 (Trpa1) in Colonic Inflammation in Dextran Sulfate Sodium (Dss)-Induced Murine Colitis. Gastroenterology 150(4): S52-S53, 2016

Superoxide generation and leukocyte accumulation: key elements in the mediation of leukotriene B₄-induced itch by transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1. Faseb Journal 27(4): 1664-1673, 2013

Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice. American Journal of Physiology. Gastrointestinal and Liver Physiology 298(1): G81-G91, 2010

Bimodal concentration-response of nicotine involves the nicotinic acetylcholine receptor, transient receptor potential vanilloid type 1, and transient receptor potential ankyrin 1 channels in mouse trachea and sensory neurons. Journal of Pharmacology and Experimental Therapeutics 347(2): 529-539, 2013

Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice. Journal of Cellular and Molecular Medicine 2019, 2019

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis. Molecular Pain 13: 1744806917705564, 2018

Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma. Journal of Biological Chemistry 291(48): 24866-24879, 2016

Contribution of transient receptor potential ankyrin 1 to chronic pain in aged mice with complete Freund's adjuvant-induced arthritis. Arthritis and Rheumatology 66(9): 2380-2390, 2014

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice. American Journal of Physiology. Gastrointestinal and Liver Physiology 304(11): G1002-G1012, 2013

Propofol restores transient receptor potential vanilloid receptor subtype-1 sensitivity via activation of transient receptor potential ankyrin receptor subtype-1 in sensory neurons. Anesthesiology 114(5): 1169-1179, 2011

The transient receptor potential ankyrin-1 mediates mechanical hyperalgesia induced by the activation of B 1 receptor in mice. Biochemical Pharmacology 125: 75-83, 2016