A low-cost, sterilizable and unobtrusive instrumentation device was developed to quantify and study the loss-of-resistance technique in epidural anesthesia. In the porcine study, the rapid fall of the applied force, plunger displacement and fluid pressure, and the oral indication of the anesthesiologists were shown to be consistent with the loss-of-resistance. A model based on fluid leakage was developed to estimate the pressure from the force and displacement measurements, so that the pressure sensor could be omitted in human studies. In both human (in vivo) and porcine (in vitro) subjects, we observed that the ligamentum flavum is less amenable to saline injection than the interspinous ligament.