Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflam...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-05, Vol.395 (4), p.572-576
Main Authors: Tong, Wei, Wang, Wei, Huang, Jing, Ren, Ning, Wu, Sheng-Xi, Li, Yong-Qi
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
ANTIBODIES
Bone cancer pain
Bone Neoplasms - complications
Bone Neoplasms - metabolism
CARCINOMAS
Disease Models, Animal
Female
HEAT
High-mobility group box 1
HMGB1 Protein - metabolism
INFLAMMATION
INOCULATION
Interleukin-1beta - metabolism
LYMPHOKINES
MAMMARY GLANDS
Pain - etiology
Pain - metabolism
Rat
RATS
Rats, Wistar
RECEPTORS
SPINAL CORD
Spinal Cord - metabolism
Spinal Cord - physiopathology
Stress, Mechanical
Synaptic Transmission
TIBIA
Toll like receptors
TUMOR CELLS
Up-Regulation
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Summary:Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.04.086