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We performed this study to quantify the detrimental effect of intraneural injection of 50 μL of saline, articaine 2%, or articaine 4% in the rat sciatic nerve.Lumbar-evoked electrospinograms from stimulation of the sciatic nerve were recorded before and immediately after injection and again after 3 weeks. Test substance was injected into the right sciatic nerve, and the untreated left sciatic nerve served as control. The animals were killed after the 3-week follow-up, and cross-sections of the sciatic nerve were examined stereologically.The evoked spinal cord field potential in the articaine groups faded away immediately after injection and was concentration-dependently, significantly more reduced at the 3-week follow-up in comparison with the saline group. The response from the control sides was unaffected in all groups. The number of myelinated axons was unaffected by the treatment. The mean cross-sectional axon area and the mean myelin sheath thickness were significantly reduced in animals injected with articaine 4%.These observations indicate concentration-dependent neurotoxic injuries after injection of articaine with a significant difference between 2% and 4% formulations. The mechanical injury of needle penetration with saline injection had no significant effect on nerve conduction or histomorphology.