Song, Zhenpeng, Xiong, Bingrui, Guan, Xue-Hai, Cao, Fei, Manyande, Anne, Zhou, Yaqun, Zheng, Hua and Tian, Yu-Ke (2016) Minocycline attenuate bone cancer pain in rats by inhibiting NFkB in spinal astrocytes. Acta Pharmacologica Sinica, 37 (6). pp. 753-762. ISSN 1671-4083
Minocycline attenuates bone cancer pain in rats by inhibiting NF-kB in spinal astrocytes - Zhen-peng Song et al 2016.pdf - Published Version
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To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.
A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro.
BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus.
Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.
|Additional Information:||© 2016 Shanghai Institute of Materia Medica, CAS|
|Subjects:||Medicine and health > Clinical medicine
Medicine and health
|Depositing User:||Anne Manyande|
|Date Deposited:||10 Jun 2016 18:21|
|Last Modified:||07 Feb 2017 13:05|
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