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. 2017 Jun 21;7:4005. doi: 10.1038/s41598-017-04198-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Intrathecal injection of CaMKII specific-inhibitor AIP2 attenuates TCI-induced cancer pain and p-CREB up-regulation. Intrathecal injection of AIP2 significantly delayed or attenuated TCI-induced mechanical allodynia (A and C), thermal hyperalgesia (B and D), spontaneous flinches (E) and limb uselessness (F) in bone cancer rats. AIP2 (10 μM/10 μl, i.t.) or PBS (vehicle control, 10 μl, i.t.) was administered once daily on days 5, 6 and 7 (A and B) or days 12, 13 and 14 (C–F) after TCI. Behavioral tests were performed 4 hours after each injection. *P < 0.05, **P < 0.01 vs sham + PBS group; ^# P < 0.05, ^## P < 0.01 vs TCI + PBS group; n = 8 for each group. (G and H) Inhibitory effect of AIP2 on p-CREB expression in TCI rats on day 7 or day 14. AIP2 (10 μM/10 μl, i.t.) or PBS (10 μl, i.t.) were administered once daily on days 5, 6 and 7 (G) or days 12, 13 and 14 (H) after TCI. L4-L6 spinal tissues were collected 4 hours after the last injection. **P < 0.01 vs sham + PBS group; ^# P < 0.05 vs TCI + PBS group; n = 4 for each group.