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Involvement of chemokine CXCL 11 in the development of morphine tolerance in rats with cancer‐induced bone pain
Author(s) -
Guo Genhua,
Peng Yawen,
Xiong Bingrui,
Liu Daiqiang,
Bu Huilian,
Tian Xuebi,
Yang Hui,
Wu Zhen,
Cao Fei,
Gao Feng
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13919
Subject(s) - morphine , cxcl11 , medicine , chemokine , astrocyte , drug tolerance , pharmacology , spinal cord , immunology , cxcl10 , central nervous system , inflammation , psychiatry
Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXC chemokine 11 ( CXCL 11) in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer‐induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We found that the level of CXCL 11 in lumbar spinal cord was increased during the development of morphine tolerance in cancer‐induced bone pain rats. Meanwhile, CXCL 11 was co‐localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL 11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by d , l ‐Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL 11. Finally, morphine stimulation could induce the release of CXCL 11 by cultured astrocytes and neurons in vitro . In summary, our results provide evidence that spinal CXCL 11 plays a powerful modulatory role in the development of morphine tolerance through cross‐talking between astrocytes and neurons. Read the Review series “Pain” .