| First Author | Xing X | Year | 2020 |
| Journal | Neuropharmacology | Volume | 165 |
| Pages | 107816 | PubMed ID | 31874168 |
| Mgi Jnum | J:304141 | Mgi Id | MGI:6694716 |
| Doi | 10.1016/j.neuropharm.2019.107816 | Citation | Xing X, et al. (2020) Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice. Neuropharmacology 165:107816 |
| abstractText | Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily that is involved in many neurological diseases, such as autism and pain hypersensitivity. We recently found that Cntnap2(-/-) mice showed elevated Akt-mTOR activity in the brain, and suppression of the Akt-mTOR pathway rescued the social deficit in Cntnap2(-/-) mice. In this study, we found that the dorsal root ganglion (DRG) from Cntnap2(-/-) mice also showed hyperactive Akt-mTOR signaling. Treatment with the Akt inhibitor LY94002 or the mTOR inhibitor rapamycin attenuated pain-related hypersensitivity to noxious mechanical stimuli, heat, and inflammatory substances. Further, suppression of mTOR signaling by rapamycin decreased DRG neuronal hyperexcitability. We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2(-/-) mice. Our results thus identified hyperactive Akt-mTOR signaling pathway as a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2. |
