Nociceptor Interleukin 33 Receptor/ST2 Signaling in Vibration-Induced Muscle Pain in the Rat

Álvarez, Pedro; Bogen, Oliver; Levine, Jon D.

doi:10.1016/j.jpain.2019.09.004

Cited by 11 publications

(9 citation statements)

References 36 publications

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“…However, it is noteworthy that mechanical hypersensitivity evoked by 20 ng of IL-33 in naive rats is weaker than that induced by SNI at 1 week, although this dose is similar to the amount of IL-33 expressed in the RN of SNI rats, implying some molecules excepting IL-33 may be also involved in the early development of mononeuropathic pain. Our findings are in accord with previously reported that administration of exogenous IL-33 to normal animals induces pain hypersensitivity, while blocking IL-33/ST2 signaling inhibits pathological pain [ 39 , 43 , 44 ].…”

Section: Discussionsupporting

confidence: 93%

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3

Qiu

Wang

et al. 2021

J Neuroinflammation

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Background Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. Methods In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. Results IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. Conclusions These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.

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Section: Discussionsupporting

confidence: 93%

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3

Qiu

Wang

et al. 2021

J Neuroinflammation

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“…We were particular interested in Il-33 , which has not previously been implicated in gout pain, but implicated in some other pain conditions, including neuropathic, cancer and muscle pain, etc. 18 , 19 Therefore, we set to examine the possible involvement of IL-33 in mediating the pain response of the mouse gout model.…”

Section: Resultsmentioning

confidence: 99%

“…IL-33, a member of the IL-1 family, binds to the receptor complex, consisting of IL-33 specific ST2 and IL-1 receptor accessory protein IL-1RAcp, to elicit biological functions in inflammation, autoimmune response and homeostasis 16 , 17 . Recent evidence suggests that IL-33 can act as an important pain mediator in certain pain conditions, including joint pain, bone cancer pain, muscle pain and neuropathic pain 12 , 18 , 19 . Our recent work further identified IL-33 engages with ST2 in peripheral sensory neurons to exert sensory neuron hyperexcitability 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

Yin

Liu

et al. 2020

Theranostics

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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, Ca 2+ imaging, reactive oxygen species (ROS) generation, neutrophil influx and nocifensive behavioral assays, etc. were used. Results: We found interleukin-33 (IL-33) was among the top up-regulated cytokines in the inflamed ankle. Neutralizing or genetic deletion of IL-33 or its receptor ST2 (suppression of tumorigenicity) significantly ameliorated pain hypersensitivities and inflammation. Mechanistically, IL-33 was largely released from infiltrated macrophages in inflamed ankle upon MSU stimulation. IL-33 promoted neutrophil influx and triggered neutrophil-dependent ROS production via ST2 during gout, which in turn, activated transient receptor potential ankyrin 1 (TRPA1) channel in dorsal root ganglion (DRG) neurons and produced nociception. Further, TRPA1 channel activity was significantly enhanced in DRG neurons that innervate the inflamed ankle via ST2 dependent mechanism, which results in exaggerated nociceptive response to endogenous ROS products during gout. Conclusions: We demonstrated a previous unidentified role of IL-33/ST2 in mediating pain hypersensitivity and inflammation in a mouse gout model through promoting neutrophil-dependent ROS production and TRPA1 channel activation. Targeting IL-33/ST2 may represent a novel therapeutic approach to ameliorate gout pain and inflammation.

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“…The percentage decrease in Tmem120A expression was calculated as: (normalized density for AS/normalized density for MM x 100) À 100. 3,5…”

Section: Sds-page and Western Blottingmentioning

confidence: 99%

Involvement of TACAN, a Mechanotransducing Ion Channel, in Inflammatory But Not Neuropathic Hyperalgesia in the Rat

Bonet

Araldi

Bogen

et al. 2021

The Journal of Pain

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Nociceptor Interleukin 33 Receptor/ST2 Signaling in Vibration-Induced Muscle Pain in the Rat

Cited by 11 publications

References 36 publications

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3

IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain

Involvement of TACAN, a Mechanotransducing Ion Channel, in Inflammatory But Not Neuropathic Hyperalgesia in the Rat

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