P2X7 receptor-deficient mice are susceptible to bone cancer pain.
P2X7 receptor-deficient mice are susceptible to bone cancer pain.
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DOI：
10.1016/j.pain.2011.03.024
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发表时间：
2011-08
期刊：
影响因子：
7.4
通讯作者：
Heegaard AM
中科院分区：
文献类型：
--
作者：
Hansen RR;Nielsen CK;Nasser A;Thomsen SIM;Eghorn LF;Pham Y;Schulenburg C;Syberg S;Ding M;Stojilkovic SS;Jorgensen NR;Heegaard AM
嘌呤能P2 X7受体参与神经性疼痛和炎性疼痛，并已被认为是疼痛治疗的可能靶点。然而，P2 X7受体在骨癌疼痛中的具体作用尚不清楚。我们证明了BALB/cJ P2 X7受体敲除（P2 X7 R KO）小鼠对骨癌疼痛易感，而且与携带癌症的野生型小鼠相比，疼痛相关行为的发作更早。此外，选择性P2 X7受体拮抗剂A-438079的急性治疗未能缓解具有和不具有星形胶质细胞活化的骨癌疼痛模型（分别接种4 T1乳腺癌细胞或NCTC 2472骨肉瘤细胞的BALB/cJ或C3 H小鼠）中的疼痛相关行为，表明星形胶质细胞P2 X7受体在骨癌疼痛中的作用可忽略不计。结果支持这一假设，即骨癌疼痛是一个独立的疼痛状态相比，神经性和炎症性疼痛。然而，最近发现的P2 X7受体剪接变异体在用于本研究的敲除小鼠中表达，使结果的解释复杂化。P2 X7剪接变体受体在脊髓中检测到，但在P2 X7 R KO小鼠的破骨细胞中未检测到。需要进一步的实验来阐明P2 X7受体在骨癌疼痛中的确切作用。疼痛相关行为在患有骨癌的P2 X7受体缺陷小鼠中较早发生，A-438079治疗未能缓解疼痛相关行为。
The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state compared with those of neuropathic and inflammatory pain. However, the recent discovery of a P2X7 receptor splice variant expressed in the knockout mice used for this study complicates the interpretation of the results. The P2X7 splice variant receptor was detected in the spinal cord but not in osteoclasts of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain. Pain-related behaviours had an earlier onset in bone cancer-bearing, P2X7 receptor-deficient mice, and treatment with A-438079 failed to alleviate pain-related behaviours.
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DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
DOI：
10.1615/critreveukaryotgeneexpr.v13.i24.150
发表时间：
2003-01-01
影响因子：
1.6
作者：
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通讯作者：
Gallagher, JA
影响因子：
6.2
作者：
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通讯作者：
Bowler, WB
影响因子：
2.8
作者：
Clohisy, DR;Ogilvie, CM;Ramnaraine, MLR
通讯作者：
Ramnaraine, MLR
影响因子：
11.5
作者：
Coleman, Robert E.
通讯作者：
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