Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice

Zhao, Jingang; Zhang, H.; Liu, S.-B.; Han, Ping; Hu, Song; Li, Q.; Wang, Z.-F.; Mao-Ying, Qi-Liang; Chen, H.-M.; Jiang, Jinju; Wu, Gen-Cheng; Mi, Wen-Li; Wang, Y.-Q.

doi:10.1016/j.neuroscience.2013.08.026

Cited by 48 publications

(42 citation statements)

References 38 publications

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“…Our recent study demonstrated that spinal IL-33 is predominantly located in astrocytes [19], whereas the distribution of ST2 in the central nervous system is disputed. ST2 has been reported to be expressed in astrocytes, but not in microglia or neurons in the brain [40].…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

et al. 2015

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Although acupuncture is widely used to manage pain, it remains highly controversial, largely due to the lack of a clear mechanism for its benefits. Here, we investigated the role of IL-33, a novel interleukin (IL)-1 family member, and its receptor ST2 in the analgesic effects of electroacupuncture (EA) on formalin-induced inflammatory pain. The results showed that 1) EA stimulation of ipsilateral Zusanli (ST 36) and Yanglingquan (GB 34) acupoints for 30 min remarkably suppressed the two phases of formalin-induced spontaneous pain; 2) subcutaneous or intrathecal administration of recombinant IL-33 (rIL-33) significantly inhibited the analgesic effect of EA, whereas the ST2 antibody potentiated EA analgesia in formalin mice; 3) EA treatment decreased the up-regulation of IL-33 and ST2 protein following formalin injection; and 4) the suppression of the formalin-induced expression of spinal phosphorylated ERK and JNK induced by EA treatment was significantly attenuated following subcutaneous rIL-33 delivery, and was further decreased by the ST2 antibody. These data suggest that EA alleviates formalin-induced inflammatory pain, at least partially, by inhibiting of spinal IL-33/ST2 signaling and the downstream ERK and JNK pathways.

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Section: Discussionmentioning

confidence: 99%

“…Our recent studies demonstrated that spinal IL-33 and its receptor ST2 mediated formalin-induced acute inflammatory pain and 4T1 carcinoma cells inoculation-induced chronic bone cancer pain in mice [18,19]. Whether IL-33 and its receptor ST2 are regulated in EA analgesia during inflammatory pain has not yet been examined.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

et al. 2015

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“…The surgical procedure was performed as described in our and other previous studies 11, 59 . Briefly, rats were anesthetized with pentobarbital sodium (50 mg/kg i.p.).…”

Section: Methodsmentioning

confidence: 99%

Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain

Zhang

et al. 2017

Sci Rep

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We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI. Intrathecal delivery of CXCR4 siRNA or CaMKII inhibitor AIP2 abrogated TCI-induced pain hypersensitivity and TCI-induced increase in p-CaMKII and p-CREB expression. Intrathecal injection of the principal ligand for CXCR4, SDF-1, promoted p-CaMKII and p-CREB expression in naive rats, which was prevented by post-administration of CXCR4 inhibitor Plerixafor or PLC inhibitor U73122. Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.

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“…7,11,13,43 In addition, astrocytosis and microglia activation, internalization of the substance P receptor, c-Fos expression and proinflammatory cytokine interleukin-1 (IL-1) beta, tumor necrosis factor-alpha, 26 IL-18, 56 IL-33, 59 and IL-6 which are the cellular and neurochemical characteristics of chronic pain, can be detected in the spinal dorsal horn or DRG. 7,10,26,43,56,59 Our previous report describes the effect of endogenous MOR ligands in the spinal cord and indicates that downregulated spinal endomorphin 2 is an important contributor to the neuropathological process of bone cancer pain. 4 Neuroinflammation appears to be involved in the peripheral nerves, DRG and the spinal cord, all of which contribute to the complex properties of bone cancer pain.…”

Section: Discussionmentioning

confidence: 99%

Neuron-restrictive silencer factor–mediated downregulation of μ-opioid receptor contributes to the reduced morphine analgesia in bone cancer pain

Zhu

Tang

Ding

et al. 2017

Pain

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Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice

Cited by 48 publications

References 38 publications

Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain

Neuron-restrictive silencer factor–mediated downregulation of μ-opioid receptor contributes to the reduced morphine analgesia in bone cancer pain

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