Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain.
Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain.
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DOI：
10.1016/j.phrs.2011.03.007
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发表时间：
2011-07
影响因子：
9.3
通讯作者：
Seybold, Virginia S.
中科院分区：
文献类型：
--
作者：
Khasabova, Iryna A.;Chandiramani, Anisha;Harding-Rose, Catherine;Simone, Donald A.;Seybold, Virginia S.
Metastatic and primary bone cancers are usually accompanied by severe pain that is difficult to manage. In light of the adverse side effects of opioids, manipulation of the endocannabinoid system may provide an effective alternative for the treatment of cancer pain. The present study determined that a local, peripheral increase in the endocannabinoid 2-arachidonoylglycgerol (2-AG) reduced mechanical hyperalgesia evoked by the growth of a fibrosarcoma tumor in and around the calcaneous bone. Intraplantar (ipl) injection of 2-AG attenuated hyperalgesia (ED50 of 8.2 μg) by activation of peripheral CB2 but not CB1 receptors and had an efficacy comparable to that of morphine. JZL184 (10 μg, ipl.), an inhibitor of 2-AG degradation, increased the local level of 2AG and mimicked the antihyperalgesic effect of 2-AG, also through a CB2 receptor-dependent mechanism. These effects were accompanied by an increase in CB2 receptor protein in plantar skin of the tumor-bearing paw as well as an increase in the level of 2AG. In naïve mice, intraplantar administration of the CB2 receptor antagonist AM630 did not alter responses to mechanical stimuli demonstrating that peripheral CB2 receptor tone does not modulate mechanical sensitivity. These data extend our previous findings with anandamide in the same model and suggest that the peripheral endocannabinoid system is a promising target for the management of cancer pain.
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DOI：
10.1111/j.1460-9568.2008.06556.x
发表时间：
2009-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Chizhmakov I;Mamenko N;Volkova T;Khasabova I;Simone DA;Krishtal O
通讯作者：
Krishtal O
影响因子：
64.8
作者：
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通讯作者：
Piomelli, D
影响因子：
15.9
作者：
Casanova, ML;Blázquez, C;Guzmán, M
通讯作者：
Guzmán, M
影响因子：
11.5
作者：
Coleman, Robert E.
通讯作者：
Coleman, Robert E.
影响因子：
6.2
作者：
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通讯作者：
SIKIC, BI