Effects of inhibiting the PI3K/Akt/mTOR signaling pathway on the pain of sciatic endometriosis in a rat model
| Autor: | Xuying Qin, Xiaofen Lu, Yan Liu, Jie Jiang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Physiology Morpholines Rat model Endometriosis Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Sciatica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) medicine Animals Phosphatidylinositol Protein kinase B Injections Spinal PI3K/AKT/mTOR pathway Pain Measurement Pharmacology Behavior Animal TOR Serine-Threonine Kinases MTOR signaling pathway General Medicine medicine.disease Sciatic Nerve Rats Disease Models Animal 030104 developmental biology nervous system chemistry Chromones Cancer research Female Behavior Observation Techniques Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 97:963-970 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2019-0156 |
| Popis: | This study investigated the relationship between the pain of sciatic endometriosis and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Adult female Sprague–Dawley rats successfully received sciatic endometriosis induction. Mechanical paw withdrawal threshold and paw withdrawal latency were recorded to assess the mechanical hypersensitivity and thermal hyperalgesia. Quantitative real-time PCR, Western blotting, and enzyme-linked immunosorbent assays were used to detect PI3K, Akt, and mTOR expressions and their phosphorylation as well as the expressions of substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF). Mechanical paw withdrawal threshold and paw withdrawal latency significantly decreased after sciatic endometriosis induction in rats; this decrease was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. Compared with controls, rats with sciatic endometriosis showed increased PI3K, Akt, and mTOR expressions and elevated p-PI3K, p-Akt, and p-mTOR protein expressions. Higher NGF, substance P, and CGRP expressions were also found in the superficial dorsal horn of the spinal cord in rats with sciatic endometriosis than in control rats 21 days after surgery. Following the injection of LY294002 into rats with sciatic endometriosis, there was a significant decrease in the expressions of NGF, substance P, and CGRP. In conclusion, the inhibition of the PI3K/Akt/mTOR signaling pathway may alleviate endometriosis-associated sciatic nerve pain in a rat model of sciatic endometriosis. |
| Databáze: | OpenAIRE |
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