Chemokines and Their Receptors: Potential Therapeutic Targets for Bone Cancer Pain

Zhou, Ya‐Qun; Gao, Hengyi; Guan, Xue-Hai; Fang, Guangguang; Chen, Yuan; Ye, Dawei

doi:10.2174/1381612821666150831141931

Cited by 36 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, our previous study verified that the chemokines CXCL10 and its receptor CXCR3 were markedly elevated in CIBP (Guan et al, 2015;Ye et al, 2014;Zhou et al, 2015). Moreover, recent studies also demonstrated that CXCR3 could express on the surface of CD8 + T cells (Laragione et al, 2011;Tokuriki et al, 2002).…”

Section: Discussionsupporting

confidence: 58%

See 1 more Smart Citation

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain

Shi

Zhou

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8 T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8 T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8 T cells.

show abstract

Section: Discussionsupporting

confidence: 58%

“…According to the literatures (Helferich et al, 2008) Guan et al, 2015;Ke et al, 2013;Liu et al, 2013;Xu et al, 2013;Yang et al, 2015), all experiments were…”

Section: Animalsmentioning

confidence: 99%

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain

Shi

Zhou

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Under BCP conditions, astrocytes become reactive, and this alters their morphology and increases GFAP expression. Activated astrocytes release a range of pro-inflammatory cytokines (eg, IL-1β) and chemokines (eg, CXCL1), which thus induces neuronal sensitization [7,[34][35][36][37] . Nevertheless, astrocytes also express receptors for these cytokines, and a positive feedback loop is consequently established.…”

Section: Bcp Induced By Walker 256 Mammary Carcinoma Cell Inocula Tionmentioning

confidence: 99%

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

show abstract

“…Moreover, Singh et al found that the CXCR5-CXCL13 axis may be involved in the cell migration, invasion, and adhesion of prostate cancer [38]. On the other hand, the alterations of chemokines expression combined with chemokines receptors may be associated with the generation and maintenance of neuropathic pain or chronic pain, and the up-regulation of chemokines in the spinal cord has been reported to be essential to the development of cancer pain [39,40]. CXCL1 has been reported to be up-regulated in astrocytes after spinal nerve ligation and contribute to the maintenance of neuropathic pain, and the increased CXCL1 expression may be involved in CIBP development [41].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain

et al. 2016

View full text Add to dashboard Cite

BackgroundThe aim of this study was to investigate the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone pain (CIBP).Material/MethodsWe established a rat CIBP model and a rat CIBP-morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13, neutralizing anti-CXCL13, and normal saline, while the control group rats underwent a sham operation and were injected with normal saline. The morphine analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) at various time points. The co-expressions of CXCL13 and NeuN were measured by immunofluorescence double-staining. CXCL13 protein and mRNA expressions were detected by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively.ResultsCompared to the sham-operation (S) group, the BM group showed obviously decreased MWT and increased MWD on Day 9 after CIBP, but obviously increased MWT and decreased MWD on Day 3 after morphine administration; subsequently, the MWT was decreased and MWD was increased (all P<0.05). In comparison with the S+saline group, increased MWT and decreased MWD were observed in BM rats on Day 3 after anti-CXCL13 administration, and obviously decreased MWT and increased MWD were found in BM rats on Day 3 after rmCXCL13 administration (all P<0.05).ConclusionsUp-regulated CXCL13 has a negative role in morphine analgesia in relief of CIBP, which may provide a new target for the management of CIBP.

show abstract

Chemokines and Their Receptors: Potential Therapeutic Targets for Bone Cancer Pain

Cited by 36 publications

References 0 publications

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain

Contact Info

Product

Resources

About