期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 98, 期 2, 页码 188-195出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2010.12.027
关键词
G-CSF; ERK; JNK; p38; PI3K; Spinal; Pain; Hyperalgesia; Nociception; Hot plate; Morphine; Opioid
资金
- Fundo de Apoio ao Ensino Pesquisa e Extensao/Universidade Estadual de Londrina [FAEPE/UEL 01/2009]
- Fundacao Araucaria
- Conselho Nacional de Pesquisa (CNPq)
- Coordenadoria de aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil
Granulocyte-colony stimulating factor (G-CSF) is a current pharmacological approach to increase peripheral neutrophil counts after anti-tumor therapies. Pain is most relevant side effect of G-CSF in healthy volunteers and cancer patients. Therefore, the mechanisms of G-CSF-induced hyperalgesia were investigated focusing on the role of spinal mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated kinase). JNK (Jun N-terminal Kinase) and p38, and PI3K (phosphatidylinositol 3-kinase). G-CSF induced dose (30-300 ng/paw)-dependent mechanical hyperalgesia, which was inhibited by local post-treatment with morphine. This effect of morphine was reversed by naloxone (opioid receptor antagonist). Furthermore, G-CSF-induced hyperalgesia was inhibited in a dose-dependent manner by intrathecal pre-treatment with ERK (PD98059), JNK (SB600125), p38 (SB202190) or PI3K (wortmanin) inhibitors. The co-treatment with MAP kinase and PI3K inhibitors, at doses that were ineffective as single treatment, significantly inhibited G-CSF-induced hyperalgesia. Concluding, in addition to systemic opioids, peripheral opioids as well as spinal treatment with MAP kinases and PI3K inhibitors also reduce G-CSF-induced pain. (C) 2011 Elsevier Inc. All rights reserved.
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