Intrathecal Injection of JWH-015 Attenuates Bone Cancer Pain Via Time-Dependent Modification of Pro-inflammatory Cytokines Expression and Astrocytes Activity in Spinal Cord
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- 作者：Cui’e Lu ; Yue Liu ; Bei Sun ; Yu’e Sun ; Bailing Hou ; Yu Zhang ; Zhengliang Ma…
- 关键词：bone cancer pain ; CB2 ; astrocytes ; pro ; inflammatory cytokines ; time ; dependent
- 刊名：Inflammation
- 出版年：2015
- 出版时间：October 2015
- 年：2015
- 卷：38
- 期：5
- 页码：1880-1890
- 全文大小：2,819 KB
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21.Pertwee, R.G., A.C. Howlett, M.E. Abood, S.P. Alexander, V. Di Marzo, M.R. Elphick, P.J. Greasley, H.S. Hansen, G. Kunos, K. Mackie, R. Mechoulam, and R.A. Ross. 2010. International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB(1) and CB(2). Pharmacological Reviews 62: 588-31.PubMed Central CrossRef - 作者单位：Cui’e Lu (1)
Yue Liu (1)
Bei Sun (1)
Yu’e Sun (1)
Bailing Hou (1)
Yu Zhang (1)
Zhengliang Ma (1)
Xiaoping Gu (1)
1. Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu Province, China - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Rheumatology
Internal Medicine
Pharmacology and Toxicology
Pathology - 出版者：Springer Netherlands
- ISSN：1573-2576
文摘
Cannabinoid receptor type 2 (CB2) agonists display potential analgesic effects in acute and neuropathic pain. However, its complex cellular and molecular mechanisms in bone cancer pain remain unclear. And less relevant reports concerned its time-dependent effects on the long-lasting modifications of behavior, spinal inflammatory cytokines levels, astrocytes activity induced by bone cancer pain. A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells was utilized. Pain behaviors at different time points were assessed by ambulatory pain scores and paw withdrawal mechanical threshold (PWMT). Pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor alpha (TNF-α), were quantitated by Western blots. Glial activity was assessed by immunohistochemistry. Intra-tibia inoculation of Walker 256 mammary gland carcinoma cells induced progressive bone cancer pain; a long-term up-regulation of IL-1β, IL-6, IL-18, and TNF-α; and the activation of glia in spinal cord. Activation of microglia was first evident on day 4 after surgery and reached to a peak on day 7 while activation of astrocytes was on day 10. A single intrathecal injection of JWH-015 attenuated bone cancer induced spontaneous pain and mechanical allodynia, reduced the expression of pro-inflammatory cytokines, and inhibited the activity of astrocytes. All the modifications were transient and peaked at 24 h after JWH-015 administration. Furthermore, the protective effects of JWH-015 were reversed in the presence of CB2-selective antagonist AM630. Overall, our results provided evidences for the persistent participation of inflammation reaction in the progression of bone cancer pain, and demonstrated that JWH-015 reduced the expression of IL-1β, IL-6, IL-18, and TNF-α and inhibited astrocytes activation in a time-dependent manner, thereby displaying an analgesic effect. KEY WORDS bone cancer pain CB2 astrocytes pro-inflammatory cytokines time-dependent