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Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats
- Source :
- Molecular Brain, Molecular Brain, Vol 5, Iss 1, p 16 (2012)
- Publication Year :
- 2012
-
Abstract
- It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP), which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4) induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker), and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol) or minocycline (an inhibitor of microglia, 100 μg) has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t.) also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.
- Subjects :
- Time Factors
(+)-Naloxone
Pharmacology
lcsh:RC346-429
Neuroinflammation
Glial activation
CD11b Antigen
Microglia
Glial fibrillary acidic protein
biology
Behavior, Animal
Posterior Horn Cells
medicine.anatomical_structure
Spinal Cord
Hyperalgesia
Cytokines
Female
medicine.symptom
Astrocyte
Pain Threshold
Pain
Bone Neoplasms
Cellular and Molecular Neuroscience
Threshold of pain
Glial Fibrillary Acidic Protein
medicine
Animals
RNA, Messenger
Carcinoma 256, Walker
Rats, Wistar
Molecular Biology
lcsh:Neurology. Diseases of the nervous system
Inflammation
Tibia
business.industry
Research
Hypertrophy
Toll-like receptor 4
Rats
Gene Expression Regulation
Astrocytes
biology.protein
TLR4
Rat
Cancer induced pain
business
Neuroscience
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 17566606
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular brain
- Accession number :
- edsair.doi.dedup.....75f3b39973a5f62c0077a28972245622