The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory cytokine and chemokine in rat trigeminal ganglia

Chung, Man‐Kyo; Asgar, Jamila; Lee, J.; Shim, Mi-Ja; Dumler, C.; Ro, Jin Y.

doi:10.1016/j.neuroscience.2015.03.067

Cited by 39 publications

(46 citation statements)

References 42 publications

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“…Which, then, are the possible mechanisms of H 2 O 2 ‐induced activation of nociceptors? Either direct receptor activation by H 2 O 2 or indirect mechanismssuch as the formation of downstream lipid peroxidation products activating TRP channels or increased expression of pro‐inflammatory cytokines and chemokines might explain the actions of H 2 O 2 (Keeble et al ., ; Chung et al ., ). Direct activation of TRPA1 channels by H 2 O 2 is mediated by H 2 O 2 ‐derived hydroxyl radicals (see Ogawa et al ., ).…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

Antinociception by the anti‐oxidized phospholipid antibody E06

Mohammadi

Oehler

Kloka

et al. 2018

British J Pharmacology

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“…Alternatively, reactive oxygen species (ROS) released in response to tissue damage during inflammation can either directly activate TRPA1 (Macpherson et al, 2007) or could lead to the production of endogenous agonists by lipid peroxidation (Trevisani et al, 2007). Recently, we showed that ROS is released within TG following masseter inflammation, which could lead to direct or indirect activation of TRPA1 within TG (Chung, 2015). Therefore, a sustained elevation of ROS in the damage tissue could potentially maintain TRPA1 activation.…”

Section: Discussionmentioning

confidence: 99%

The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats

et al. 2015

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TRPA1 is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and NMDA-induced acute mechanical hypersensitivity and complete Freund’s adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and αβmeATP, a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain and mechanical hyperalgesisa. Mechanistic studies elucidating transcriptional or post-translational regulation of TRPA1 expression under pathological pain conditions should provide important basic information to further advance the treatment of craniofacial muscle pain conditions.

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“…ROS levels were determined using H2DCFDA (Invitrogen, Carlsbad, CA) according to the protocol previously described (Chung et al, ). Briefly, rats were injected with vehicle or complete CFA in isotonic saline into the masseter muscle.…”

Section: Methodsmentioning

confidence: 99%

“…ROS levels were determined using H2DCFDA (Invitrogen, Carlsbad, CA) according to the protocol previously described (Chung et al, 2015).…”

Section: Ros Assaymentioning

confidence: 99%

TRPM2 participates the transformation of acute pain to chronic pain during injury‐induced neuropathic pain

Wang

Song

Wang³

et al. 2019

Synapse

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Transient receptor melastatin 2 (TRPM2) is a nonselective Ca2+‐permeable cation channel highly expressed in brain and other tissues. Studies showed that TRPM2 contributed to the induction of inflammatory cytokine and chemokine of immune cells, resulted in neuropathic pain. However, how TRPM2 regulates neuropathic pain is not clear. The sciatic nerve chronic constriction injury (CCI) rat model was used to induce chronic neuropathic pain. The RNA and protein level of TRPM2 was detected with real‐time PCR and western blot. SiRNA targeting TRPM2 was used to knockdown the expression of TRPM2. Reactive oxygen species (ROS) levels were determined using H2DCFDA assay and NO production was analyzed by measuring the accumulated level of its stable metabolite (nitrite). We found that CCI significantly increased TRPM2 expression in dorsal root ganglion and spinal cord. Knockdown TRPM2 in early phase after CCI alleviated injury‐induced neuropathic pain. Mechanistically, we demonstrated that TRPM2 knockdown drastically inhibited the iNOS expression and NO generation, with decreased ROS generation in CCI rat. TRPM2 participates in the transformation of acute pain to chronic pain during injury‐induced neuropathic pain, which might serve as a potential therapeutic target for neuropathic pain.

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The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory cytokine and chemokine in rat trigeminal ganglia

Cited by 39 publications

References 42 publications

Antinociception by the anti‐oxidized phospholipid antibody E06

Antinociception by the anti‐oxidized phospholipid antibody E06

The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats

TRPM2 participates the transformation of acute pain to chronic pain during injury‐induced neuropathic pain

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