Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: in vivo study using TRPA1-deficient mice

Abstract

BackgroundThe transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable cation channel that is expressed on capsaicin-sensitive sensory neurons, endothelial and inflammatory cells. It is activated by a variety of inflammatory mediators, such as methylglyoxal, formaldehyde and hydrogen sulphide. Since only few data are available about the role of TRPA1 in arthritis and related pain, we investigated its involvement in inflammation models of different mechanisms.MethodsChronic arthritis was induced by complete Freund’s adjuvant (CFA), knee osteoarthritis by monosodium iodoacetate (MIA) in TRPA1 knockout (KO) mice and C57Bl/6 wildtype mice. For comparison, carrageenan- and CFA-evoked acute paw and knee inflammatory changes were investigated. Thermonociception was determined on a hot plate, cold tolerance in icy water, mechanonociception by aesthesiometry, paw volume by plethysmometry, knee diameter by micrometry, weight distribution with incapacitance tester, neutrophil myeloperoxidase activity and vascular leakage by in vivo optical imaging, and histopathological alterations by semiquantitative scoring.ResultsCFA-induced chronic mechanical hypersensitivity, tibiotarsal joint swelling and histopathological alterations, as well as myeloperoxidase activity in the early phase (day 2), and vascular leakage in the later stage (day 7), were significantly reduced in TRPA1 KO mice. Heat and cold sensitivities did not change in this model. Although in TRPA1 KO animals MIA-evoked knee swelling and histopathological destruction were not altered, hypersensitivity and impaired weight bearing on the osteoarthritic limb were significantly decreased. In contrast, carrageenan- and CFA-induced acute inflammation and pain behaviours were not modified by TRPA1 deletion.ConclusionsTRPA1 has an important role in chronic arthritis/osteoarthritis and related pain behaviours in the mouse. Therefore, it might be a promising target for novel analgesic/anti-inflammatory drugs.

Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms

“…and xylazine (10 mg/kg; Sedaxylan; Eurovet Animal Health B.V.) anesthesia 2 d after the paw incision. Fluorescence imaging was performed 20 min postinjection using an IVIS Lumina II in vivo optical imaging system (PerkinElmer; autoacquisition time, f/stop = 1, binning = 2, excitation: 745 nm, emission filter: >800 nm) (50).…”

“…The sections (n = 3-4 animal per group) were examined by Neurolucida software (v07; MBF Bioscience) using a Nikon Eclipse Ni-E bright-field microscope with a computer-controlled stage. A modified unbiased stereology protocol was used for quantification of glial fibrillary acidic protein (GFAP) or Iba1 immunoreactive cells along the nociceptive pathway as previously described (50).…”

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

“…The unique features of SzV-1287 compared to other SSAO inhibitors are its COX inhibitory action, without ulcerogenic effects25, and potent dual antagonistic property at the TRPV1/TRPA1 ion channels localised on peptidergic sensory nerves39, inflammatory cells40, and chondrocytes4142. The importance of TRPV1/TRPA1-dependent neurogenic inflammatory mechanisms in RA has been extensively investigated and received a great attention434445. Both receptors are a ligand-gated cation channel activated by various inflammatory mediators including protons, lipids, reactive oxygen species and lipoxygenase products, which result in the release of a broad range of neuropeptides40.…”

Sulphurous Mineral Waters: New Applications for Health

“…This receptor may therefore be a promising target for novel analgesic/anti-inflammatory drugs [89]. The interaction of hydrogen sulphide on T-Type Ca 2+ channels can serve as a therapeutic target for the treatment of intractable pain and neuronal lesions [90].…”