Enhanced SCN7A/Nax expression contributes to bone cancer pain by increasing excitability of neurons in dorsal root ganglion

Ke, Changbin; He, Weichun; Li, C.J.; Shi, Dai; Gao, Fang; Tian, Yuan

doi:10.1016/j.neuroscience.2012.09.046

Cited by 35 publications

(33 citation statements)

References 50 publications

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“…Rat BCP models were established using previously described methods [7,[23][24][25] . In brief, under anesthesia with pentobarbital sodium (40 mg/kg, ip), rats were placed in a supine position, and the right leg was shaved and disinfected with 7% iodine.…”

Section: Bcp Modelingmentioning

confidence: 99%

“…After the cells had been cultured for 10 d and reached approximately 80% confluence, the rrIL-1β was added to the medium at different concentrations (0.1, 1.0, 10.0, and 50.0 ng/mL). To examine the inhibitory effect of minocycline, the cells were pretreated with this drug (25,50,75, and 100 μmol/mL) 12 h prior to rrIL-1β stimulation. Four hours after rrIL-1β interference, the astrocytes were fixed with 4% PFA for 20 min.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Based on previous literature [5,9,23,25,30,31] , Walker 256 mammary carcinoma cell inoculation has been demonstrated to be a successful model to investigate BCP because it effectively mimics the chronic pain symptoms of patients who suffer from osteocarcinoma. Here, the tumor-bearing rats manifested mechanical tactile allodynia 14 d after tumor cell inoculation.…”

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

confidence: 99%

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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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Section: Bcp Modelingmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

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

confidence: 99%

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

et al. 2016

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“…In a large-scale gene expression study in a rat model of temporal lobe epilepsy, a persistently increased SCN7A/Nax expression in neurons and reactive astroglia was revealed, which supported the possible involvement of this channel in the epileptogenic process and hence the generation of chronic pain [95]. In addition, it has been reported [96] that implantation of cancer cells into the tibia induced bone-cancer-related pain behaviors and led to the up-regulation of SCN7A/Nax expression in medium-to large-sized DRG neurons. Depletion of SCN7A/Nax by RNAi lentivirus significantly alleviated the CIBP, whereas ectopic expression of SCN7A/ Nax contributed to depolarization of the RMP, facilitated the generation of subthreshold oscillation, and consequently increased excitability of DRG neurons.…”

Section: Scn7a/naxmentioning

confidence: 57%

New insights of nociceptor sensitization in bone cancer pain

Bai

Gao

Kong

et al. 2014

Expert Opinion on Therapeutic Targets

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Developing mechanistic therapies to treat CIBP is a challenge, but they have the potential to fundamentally change our ability to effectively block/relieve CIBP and increase the functional status and quality of life of patients with bone metastasis. Further studies are desperately needed at both the preclinical and clinical levels to determine whether the targets as mentioned in this review are viable and feasible for patient populations.

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“…[70] Recent data also suggest that the chemokine MCP-1 is involved in the etiology of bone pain induced by cancer metastasis. [71] Moreover, specific ion channels might also play an important role in this cancer pain development, such as KCNQ/M channels, [72] SCN7A/Nax ion channel, [73] and the potential involvement of Nav1.8 and Nav1.9 sodium channels. [74,75] Based on the recently acquired knowledge of nociceptive mediators released at the tumor site, blocking tumor-associated mediators, including Tumor necrosis factor beta (TNFB), [18] endothelin, [17] calcitonin gene-related peptide, [76] NGF, [34] or cyclooxygenase 2 (COX2), [77] significantly reduces tumor-induced nociception.…”

Section: Resultsmentioning

confidence: 99%

The potential therapeutic targets to bone pain induced by cancer metastasis

Wei

Shi

et al. 2013

J Can Res Ther

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About 75-90% of patients with advanced metastatic cancer experience significant cancer pain. Bone cancer pain is one of the most common pains experienced by patients with advanced breast, prostate, or lung cancer. It is characterized by significant skeletal remodeling, fractures, pain, and anemia, all of which reduce the functional status, quality of life, and survival of the patient. Recent years have seen great progress toward alleviating bone pain with the identification of a range of chemicals as well as receptors modulating cancer pain progression. However, the complicated interactions among these factors and, sometimes, the contradicting effects of the same factor in different pathways make it difficult to spot individual effective targets. The sheer quantity of the chemicals involved and the limited understanding from animal models are the constraints in the development of effective therapies for cancer bone pain. In this review, key targets will be discussed along the pain transduction pathway, including peripheral pain sensation, spinal cord transduction pathway, and the central nervous system, to offer a logical and systematic study for the development of combined anti-bone pain treatments.

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Enhanced SCN7A/Nax expression contributes to bone cancer pain by increasing excitability of neurons in dorsal root ganglion

Cited by 35 publications

References 50 publications

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

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

New insights of nociceptor sensitization in bone cancer pain

The potential therapeutic targets to bone pain induced by cancer metastasis

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