Effects of inhibiting the PI3K/Akt/mTOR signaling pathway on the pain of sciatic endometriosis in a rat model

• Published in: Canadian journal of physiology and pharmacology Vol. 97; no. 10; pp. 963 - 970
• Main Authors: Liu, Yan, Qin, Xuying, Lu, Xiaofen, Jiang, Jie
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.10.2019; Canadian Science Publishing NRC Research Press
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Behavior Observation Techniques; Behavior, Animal - drug effects; Calcitonin; Calcitonin gene-related peptide; Chromones - administration & dosage; Disease Models, Animal; Dorsal horn; douleur nerveuse sciatique; Endometriosis; Endometriosis - complications; Endometriosis - pathology; endométriose; Enzyme-linked immunosorbent assay; Enzymes; Female; Growth factors; Hyperalgesia; Hypersensitivity; Immunoassays; Injection; Injections, Spinal; Kinases; Latency; LY294002; Morpholines - administration & dosage; Nerve growth factor; Neuralgia; Pain; Pain Measurement; Pain perception; Peptides; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Physiology; PI3K/Akt/mTOR pathway; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rapamycin; Rats; Rats, Sprague-Dawley; Rodents; Sciatic nerve; Sciatic Nerve - pathology; sciatic nerve pain; Sciatica - diagnosis; Sciatica - drug therapy; Sciatica - etiology; Signal transduction; Signal Transduction - drug effects; Spinal cord; Studies; Substance P; Surgery; TOR protein; TOR Serine-Threonine Kinases - metabolism; voie de signalisation PI3K/Akt/mTOR; Western blotting; China; douleur nerveuse sciatique; LY294002; voie de signalisation PI3K/Akt/mTOR; endometriosis; endométriose; PI3K/Akt/mTOR pathway; sciatic nerve pain
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2019-0156

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.