Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability

Pereira, Ione Cristina de Paiva; Mendes, Saulo José Figueiredo; Pereira, Domingos Magno Santos; Muniz, Thayanne França; Colares, Valderlane L. P.; Monteiro, Cinara Regina Aragão Vieira; Martins, Mahiba M R de S; Grisotto, Marcos Augusto Grigolin; Monteiro-Neto, Valério; Monteiro, Sílvio Gomes; Calixto, João B.; Brain, Susan D.; Fernandes, Elizabeth S.

doi:10.3389/fphar.2017.00053

Cited by 24 publications

(20 citation statements)

References 29 publications

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“…Two non-hereditary forms of specific pain stand out in which TRPA1 is involved, the challenging-to-manage pain [89,90,[110][111][112][113][114][115][116][117] of sickle-cell disease [118,119], and the largely unmet medical need of arthritis pain.…”

Section: Trpa1 In An Inherited Episodic Pain Syndrome and Other Formsmentioning

confidence: 99%

Regulation of Pain and Itch by TRP Channels

et al. 2017

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Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1-modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accomplished via simple dosing strategies, and also by incorporating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.

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Section: Trpa1 In An Inherited Episodic Pain Syndrome and Other Formsmentioning

confidence: 99%

Regulation of Pain and Itch by TRP Channels

et al. 2017

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“…TRPA1 is mostly expressed in primary nociceptor neurons, but it was evinced in the cornea, skin, pancreas, spleen, lung, kidney, testis, and the human endometrium ( 19 ). Expression of TRPA1 channels in polymorphonuclear granulocytes of patients suffering from chronic inflammatory disease was shown to correlate with nociception ( 20 ). The role of TRPA1 is known in complete Freund’s adjuvant-induced inflammation.…”

Section: Introductionmentioning

confidence: 99%

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

et al. 2018

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Transient receptor potential ankyrin 1 (TRPA1) non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs) are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM) liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS). In the frame of the present study, we set out to compare the participation of this mechanism in antinociceptive and anti-inflammatory effects of inorganic sodium POLY and DMTS in carrageenan-evoked hind-paw inflammation. Inflammation of murine hind paws was induced by intraplantar injection of carrageenan (3% in 30 µL saline). Animals were treated intraperitoneally with POLY (17 µmol/kg) or DMTS (250 µmol/kg) or their respective vehicles 30 min prior paw challenge and six times afterward every 60 min. Mechanical pain threshold and swelling of the paws were measured by dynamic plantar aesthesiometry and plethysmometry at 2, 4, and 6 h after initiation of inflammation. Myeloperoxidase (MPO) activity in the hind paws were detected 6 h after challenge by luminescent imaging. Mice genetically lacking TRPA1 ion channels, sst4 receptors and their wild-type counterparts were used to examine the participation of these proteins in POLY and DMTS effects. POLY counteracted carrageenan-evoked mechanical hyperalgesia in a TRPA1 and sst4 receptor-dependent manner. POLY did not influence paw swelling and MPO activity. DMTS ameliorated all examined inflammatory parameters. Mitigation of mechanical hyperalgesia and paw swelling by DMTS were mediated through sst4 receptors. These effects were present in TRPA1 knockout animals, too. DMTS inhibited MPO activity with no participation of the sensory neuron–SOM axis. While antinociceptive effects of POLY are transmitted by activation of peptidergic nerves via TRPA1, release of SOM and its effect on sst4 receptors, those of DMTS partially rely on SOM release triggered by other routes. SOM is responsible for the inhibition of paw swelling by DMTS, but TRPA1 does not contribute to its release. Modulation of MPO activity by DMTS is independent of TRPA1 and sst4.

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“…ROS‐mediated activation of TRPA1 and TRPV1 channels has been suggested as the mechanism underlying painful pathologies such as rheumatoid and gouty arthritis (Trevisan et al ., ; Pereira et al ., ), as well as trigeminal neuropathic pain (Trevisan et al ., ). TRPA1 and TRPV1 channels are polymodal transmembrane cation channels, critically involved in nociception.…”

Section: Introductionmentioning

confidence: 99%

Antinociception by the anti‐oxidized phospholipid antibody E06

Mohammadi

Oehler

Kloka

et al. 2018

British J Pharmacology

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These authors contributed equally. BACKGROUND AND PURPOSEROS and their downstream molecules such as oxidized phospholipids (OxPL) and 4-hydroxynonenal activate TRPA1 and TRPV1 (vanilloid 1) cation channels in vivo and in vitro shaping thermal and mechanical hypersensitivity in inflammatory pain. E06/T15 is a monoclonal autoantibody against oxidized phosphatidylcholine (OxPC) used in diagnostics in arteriosclerosis. Recently, we provided evidence that E06 also ameliorates inflammatory pain. Here, we studied E06 for local treatment against hypersensitivity evoked by endogenous and exogenous agonists of TRPA1 or TRPV1 channels. EXPERIMENTAL APPROACHWe utilized a combination of reflexive and complex behavioural pain measurements, live-cell calcium imaging and OxPC-binding assays. The lipid peroxidation metabolite 4-hydroxynonenal, hydrogen peroxide as a source of ROS, allyl isothiocyanate and capsaicin were used to activate their respective receptors. KEY RESULTSAll irritants induced thermal and mechanical hypersensitivity, spontaneous nocifensive and affective-motivational behaviour, as well as calcium influx in HEK TRPA1 -or HEK TRPV1 -cells and dorsal root ganglion neurons. E06 prevented prolonged mechanical hypersensitivity induced by all irritants except for H 2 O 2 . E06 did not alter immediate irritant-induced nocifensive or affective motivational behaviour. In vitro, E06 blocked only 4-hydroxynonenal-induced calcium influx although this compound did not bind to E06. After 1-3 h, all tested irritants elicited formation of OxPC in paw tissue. CONCLUSIONS AND IMPLICATIONSE06 ameliorates not only inflammatory pain but also prolonged hypersensitivity due to formation of OxPC. This supports the view that neutralizing certain OxPL as endogenous activators of TRPA1 or TRPV1 channels may be valuable for pain therapy. Abbreviations

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Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability

Cited by 24 publications

References 29 publications

Regulation of Pain and Itch by TRP Channels

Regulation of Pain and Itch by TRP Channels

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

Antinociception by the anti‐oxidized phospholipid antibody E06

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