CXCR3: Latest evidence for the involvement of chemokine signaling in bone cancer pain

Guo, Genhua; Gao, Feng

doi:10.1016/j.expneurol.2015.02.003

Cited by 14 publications

(12 citation statements)

References 73 publications

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“…Repeated administration of morphine always lead to the drug tolerance, and patients may need higher doses of drug to achieve comparable pain relief ( King et al, 2005 ; Williams et al, 2013 ). Considerable advance has been made in the mechanisms underlying morphine tolerance, including desensitization and internalization of opioid receptor ( Narita et al, 2006 ; Martini and Whistler, 2007 ), heterodimers of G protein-coupled receptors ( Pasternak and Pan, 2011 ; Szentirmay et al, 2013 ), involvement of chemokines ( Ye et al, 2014 ; Guo and Gao, 2015 ; Guo et al, 2017 ; Wang et al, 2017 ), etc. However, detailed mechanisms are still far from clear and few strategies are available for the management of morphine tolerance for now.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

Liu

Zhou

Peng

et al. 2018

Front. Mol. Neurosci.

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Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer’s disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.

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Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

Liu

Zhou

Peng

et al. 2018

Front. Mol. Neurosci.

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“…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

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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.

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“…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

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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.

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CXCR3: Latest evidence for the involvement of chemokine signaling in bone cancer pain

Cited by 14 publications

References 73 publications

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

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

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