Abstract | BACKGROUND AND OBJECTIVES: METHODS: RESULTS:
Bone cancer did not alter total mTOR expression but caused significant downregulation of PTEN and upregulation of p-mTOR and p-S6K1 in spinal neurons. Rapamycin markedly reduced BCP. Upregulation of spinal PTEN by i.t. Ad-PTEN significantly relieved BCP and downregulated p-mTOR and p-S6K1; while i.t. Ad-antisense PTEN led to the opposite effects of Ad-PTEN. Spinal PPARγ expression increased in BCP rats, co-localizing mainly with neurons and a few astrocytes, but not in microglia. Pioglitazone (500 μg/day i.t. for one week, from 7 days after surgery) attenuated BCP, further increased expression of PPARγ, and inhibited downregulation of PTEN and upregulation of p-mTOR and p-S6K1 in the SDH. Pioglitazone's analgesic effect was enhanced by Ad-PTEN and attenuated by Ad-antisense PTEN. Blockade of PPARγ with GW9662 (300 μg i.t. 15 min prior to pioglitazone) reversed the effects of pioglitazone on BCP and regulations of PPARγ/PTEN/mTOR signal. CONCLUSIONS: Intrathecal pioglitazone administration alleviates BCP by regulating the PPARγ/PTEN/mTOR signal in the SDH. Our data provided new insight in the therapeutic strategy in BCP management.
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Authors | Wei Gu, Yu'e Sun, Wanjie Gu, Yulin Huang, Jinhua Bo, Luyang Zhou, Zhengliang Ma, Xiaoping Gu, Wei Zhang |
Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
(Biomed Pharmacother)
Vol. 131
Pg. 110692
(Nov 2020)
ISSN: 1950-6007 [Electronic] France |
PMID | 32942156
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. |
Chemical References |
- Analgesics
- PPAR gamma
- mTOR protein, rat
- TOR Serine-Threonine Kinases
- PTEN Phosphohydrolase
- Pten protein, rat
- Pioglitazone
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Topics |
- Analgesics
(administration & dosage)
- Animals
- Bone Neoplasms
(drug therapy, metabolism, pathology)
- Cancer Pain
(drug therapy, metabolism, pathology)
- Female
- Injections, Spinal
- PPAR gamma
(metabolism)
- PTEN Phosphohydrolase
(metabolism)
- Pioglitazone
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord Dorsal Horn
(drug effects, metabolism, pathology)
- TOR Serine-Threonine Kinases
(metabolism)
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