Prevention of Paclitaxel-Induced Allodynia by Minocycline: Effect on Loss of Peripheral Nerve Fibers and Infiltration of Macrophages in Rats

• Published in: Molecular pain Vol. 6; no. 1; p. 76
• Main Authors: Liu, Cui-Cui, Lu, Ning, Cui, Yu, Yang, Tao, Zhao, Zhi-Qi, Xin, Wen-Jun, Liu, Xian-Guo
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 05.11.2010; BioMed Central Ltd; Sage Publications Ltd; BioMed Central; SAGE Publishing
• Subjects: Activating Transcription Factor 3 - metabolism; Animals; Cell Movement - drug effects; Drug therapy; Experiments; Fluorescent Antibody Technique; Ganglia, Spinal - drug effects; Ganglia, Spinal - pathology; Health aspects; Hyperalgesia - chemically induced; Hyperalgesia - pathology; Hyperalgesia - prevention & control; Immunohistochemistry; Macrophages; Macrophages - drug effects; Macrophages - pathology; Male; Medical research; Minocycline; Minocycline - pharmacology; Nerve Fibers - drug effects; Nerve Fibers - pathology; Nervous system diseases; Neurosciences; Paclitaxel - adverse effects; Peripheral Nerves - drug effects; Peripheral Nerves - pathology; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Risk factors; Rodents; Studies; Up-Regulation - drug effects
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1186/1744-8069-6-76

Background: Although paclitaxel is a frontline antineoplastic agent for treatment of solid tumors, the paclitaxel-evoked pain syndrome is a serious problem for patients. There is currently no valid drug to prevent or treat the paclitaxel-induced allodynia, partly due to lack of understanding regarding the cellular mechanism. Studies have shown that minocycline, an inhibitor of microglia/macrophage, prevented neuropathic pain and promoted neuronal survival in animal models of neurodegenerative disease. Recently, Cata et al also reported that minocycline inhibited allodynia induced by low-dose paclitaxel (2 mg/kg) in rats, but the mechanism is still unclear. Results: Here, we investigate by immunohistochemistry the change of intraepidermal nerve fiber (IENF) in the hind paw glabrous skin, expression of macrophage and activating transcription factor 3 (ATF3) in DRG at different time points after moderate-dose paclitaxel treatment (cumulative dose 24 mg/kg; 3 × 8 mg/kg) in rats. Moreover, we observe the effect of minocycline on the IENF, macrophages and ATF3. The results showed that moderate-dose paclitaxel induced a persisted, gradual mechanical allodynia, which was accompanied by the loss of IENF in the hind paw glabrous skin and up-regulation of macrophages and ATF3 in DRG in rats. The expressions of ATF3 mainly focus on the NF200-positive cells. More importantly, we observed that pretreatment of minocycline at dose of 30 mg/kg or 50 mg/kg, but not 5 mg/kg, prevented paclitaxel-evoked allodynia. The evidence from immunohistochemistry showed that 30 mg/kg minocycline rescued the degeneration of IENF, attenuated infiltration of macrophages and up-regulation of ATF3 induced by paclitaxel treatment in rats. Conclusions: Minocycline prevents paclitaxel-evoked allodynia, likely due to its inhibition on loss of IENF, infiltration of macrophages and up-regulation of ATF3 in rats. The finding might provide potential target for preventing paclitaxel-induced neuropathic pain.