Granulocyte-Colony Stimulating Factor (G-CSF) induces mechanical hyperalgesia via spinal activation of MAP kinases and PI3K in mice

作者：Carvalho Thacyana T; Flauzino Tamires; Otaguiri Eliane S; Batistela Ana P; Zarpelon Ana C; Cunha Thiago M; Ferreira Sergio H; Cunha Fernando Q; Verri Waldiceu A Jr^*

来源：Pharmacology Biochemistry and Behavior, 2011, 98(2): 188-195.

DOI：10.1016/j.pbb.2010.12.027

• G-CSF
• ERK
• JNK
• p38
• PI3K
• Spinal
• Pain
• Hyperalgesia
• Nociception
• Hot plate
• Morphine
• Opioid

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.

• 出版日期2011-4