Propofol attenuates pain hypersensitivity and neuroinflammation in chronic constriction injury rats by regulating miR-1249-3p/VEGFA axis

Background: Neuropathic pain (NP), a disabling chronic condition with limited treatments, is recapitulated in the chronic constriction injury (CCI) rat model.The role of the miR-1249-3p/VEGFA (vascular endothelial growth factor A) axis in propofol-mediated analgesia remains unclear.Methods: AntagomiR-1249-3p, antagomiR-NC (negative control), a VEGFA-targeting siRNA, and si-NC were delivered intrathecally via lentiviral vectors 3 days before CCI.Propofol (15 mg/kg) was intraperitoneally administered for 7 consecutive days after CCI surgery.Behavioral tests assessed mechanical pain threshold and thermal pain threshold (n = 8).Spinal miR-1249-3p and VEGFA expression were detected by reverse transcription-quantitative polymerase chain reaction.Concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and IL-18 in the spinal cord were quantified using ELISA.Protein levels of VEGFA, COX2, iNOS, phospho-NF-κB p65, and total NF-κB p65 were detected using Western blotting.The relationship between miR-1249-3p and VEGFA was validated by dualluciferase reporter assay.Results: The expression of miR-1249-3p decreased and VEGFA increased in the spinal cord of CCI rats (all P < 0.001).The luciferase reporter assay demonstrated that miR-1249-3p targets VEGFA (P < 0.001).Propofol treatment upregulated miR-1249-3p (P < 0.001) and downregulated VEGFA (P < 0.001).The antinociceptive effects and suppression of pro-inflammatory markers of propofol were abolished by antagomiR-1249-3p (P < 0.001), and this abolition was rescued by VEGFA knockdown (P < 0.001).Propofol attenuates NP and neuroinflammation in CCI rats via inhibiting the NF-κB pathway through the miR-1249-3p/VEGFA axis.Conclusions: These findings suggest that propofol may reduce behavioral signs of NP and suppress associated neuroinflammation in CCI rats by the miR-1249-3p/VEGFA axis.