Alterations in opioid inhibition cause widespread nociception but do not affect anxiety-like behavior in oral cancer mice.
Alterations in opioid inhibition cause widespread nociception but do not affect anxiety-like behavior in oral cancer mice.
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DOI：
10.1016/j.neuroscience.2017.06.038
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发表时间：
2017-11-05
期刊：
影响因子：
3.3
通讯作者：
Schmidt BL
中科院分区：
文献类型：
--
作者：
Ye Y;Bernabé DG;Salvo E;Viet CT;Ono K;Dolan JC;Janal M;Aouizerat BE;Miaskowski C;Schmidt BL
癌症患者普遍存在广泛的疼痛和焦虑。我们假设，癌症伴随着内源性阿片类药物介导的抑制作用的减弱，这随后会导致广泛的疼痛和焦虑。为了验证这一假设，我们使用了舌头口腔鳞状细胞癌(SCC)的小鼠模型。我们发现，除了我们之前报道的与局部伤害性行为相关的行为外，舌鳞癌小鼠还表现出广泛的伤害性行为。舌鳞状细胞癌小鼠表现出脊髓阿片受体表达减少的模式；鞘内分别给予mU(MOR)、Delta(DOR)和Kappa(KOR)阿片受体激动剂减少了小鼠广泛的伤害性感受，但在注射MOR激动剂后甩动实验失败。我们从这些发现中推断，阿片受体对口腔癌小鼠广泛的伤害性感受起作用。尽管有明显的伤害感，但根据开场试验和高架迷宫的测量，舌鳞状细胞癌小鼠在焦虑样行为方面与假小鼠没有区别。与对照小鼠相比，癌症患者焦虑相关脑区的c-Fos染色没有显著差异。在伤害性行为和类焦虑行为之间没有发现相关性。此外，阿片受体激动剂对癌症小鼠在开阔场地和高架迷宫中测量的行为没有产生统计上显著的影响。最后，我们使用了一个急性癌症疼痛模型(将癌症上清液注射到小鼠舌头中)来测试对慢性疼痛的适应是否导致癌症小鼠没有更大的焦虑样行为。在急性癌症疼痛的小鼠中，没有观察到焦虑样行为的变化。
Widespread pain and anxiety are commonly reported in cancer patients. We hypothesize that cancer is accompanied by attenuation of endogenous opioid-mediated inhibition, which subsequently causes widespread pain and anxiety. To test this hypothesis we used a mouse model of oral squamous cell carcinoma (SCC) in the tongue. We found that mice with tongue SCC exhibited widespread nociceptive behaviors in addition to behaviors associated with local nociception that we reported previously. Tongue SCC mice exhibited a pattern of reduced opioid receptor expression in the spinal cord; intrathecal administration of respective mu (MOR), delta (DOR), and kappa (KOR) opioid receptor agonists reduced widespread nociception in mice, except for the fail flick assay following administration of the MOR agonist. We infer from these findings that opioid receptors contribute to widespread nociception in oral cancer mice. Despite significant nociception, mice with tongue SCC did not differ from sham mice in anxiety-like behaviors as measured by the open field assay and elevated maze. No significant differences in c-Fos staining were found in anxiety-associated brain regions in cancer relative to control mice. No correlation was found between nociceptive and anxiety-like behaviors. Moreover, opioid receptor agonists did not yield a statistically significant effect on behaviors measured in the open field and elevated maze in cancer mice. Lastly, we used an acute cancer pain model (injection of cancer supernatant into the mouse tongue) to test whether adaptation to chronic pain is responsible for the absence of greater anxiety-like behavior in cancer mice. No changes in anxiety-like behavior were observed in mice with acute cancer pain.
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影响因子：
8.8
作者：
Hammerlid, E;Ahlner-Elmqvist, M;Bjordal, K;Biörklund, A;Evensen, J;Boysen, M;Jannert, M;Kaasa, S;Sullivan, M;Westin, T
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影响因子：
2.5
作者：
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通讯作者：
Chichorro, Juliana Geremias
影响因子：
7.4
作者：
HEIM, HM;OEI, TPS
通讯作者：
OEI, TPS
C57BL/6J 和 BALB/cJ 小鼠焦虑样行为和社交行为的应变和性别差异
影响因子：
2.4
作者：
An, Xiao-Lei;Zou, Jun-Xian;Broders, Hugh
通讯作者：
Broders, Hugh
影响因子：
3.4
作者：
Brintzenhofe-Szoc, Karlynn M.;Levin, Tomer T.;Zabora, James R.
通讯作者：
Zabora, James R.