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5 nM). Thus, this work offers a simple and efficient strategy to fabricate a highly effective SERS structure with broad applications in environmental science, analytical chemistry, etc. Electrical preferential activation of small nociceptive fibers may be achieved with the use of specialized small area electrodes, however, the existing electrodes are limited to low stimulation intensities. As existing electrodes have been developed empirically, the present study aimed to use computational modeling and optimization techniques to investigate if change