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Effects of Early General Anesthetic Exposure on Susceptibility to Chronic Pain by Enhancement of Neural Activity via Mammalian Target of Rapamycin Pathway
Li, Q.; Mathena, R.P.; Li, F.; Dong, X.; Guan, Y.; Mintz, C.D. Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway. Int. J. Mol. Sci.2023, 24, 13760.
Li, Q.; Mathena, R.P.; Li, F.; Dong, X.; Guan, Y.; Mintz, C.D. Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway. Int. J. Mol. Sci. 2023, 24, 13760.
Li, Q.; Mathena, R.P.; Li, F.; Dong, X.; Guan, Y.; Mintz, C.D. Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway. Int. J. Mol. Sci.2023, 24, 13760.
Li, Q.; Mathena, R.P.; Li, F.; Dong, X.; Guan, Y.; Mintz, C.D. Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway. Int. J. Mol. Sci. 2023, 24, 13760.
Abstract
Patients who have undergone surgery in early life may be at elevated risk for neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to general anesthetic (GA) causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 (P7) and underwent spared nerve injury at P28 which causes chronic pain. Selected groups were treated with rapamycin, an mTOR inhibitor, for eight weeks. Behavioral tests show early isoflurane exposure enhances susceptibility to chronic pain, and rapamycin treatment improves outcomes. Immunohistochemistry, Western blotting, and q-PCR indicates that isoflurane upregulates mTOR expression and neural activity in DSC and DRG. Accompanying upregulation of mTOR and rapamycin-reversible changes in chronic pain-associated markers, including N-cadherin, cAMP response element-binding protein (CREB), purinergic P2Y12 receptor, glial fibrillary acidic protein (GFAP) in DSC; and connexin 43, phospho-extracellular signal-regulated kinase (p-ERK), GFAP, Iba1 in DRG, were observed. We conclude that early GA exposure alters the development of pain circuits such that mice are subsequently more vulnerable to chronic neuropathic pain states.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
