This Phase I SBIR develops the Locally Targeted Acoustic (LTA) Neuropathy Medication Delivery System to effectively provide localized analgesia via direct transdermal delivery of medications to target nerves ? improving efficacy and eliminating both wasted/discarded drug and the negative side effects associated with oral/systemic delivery. Public Health Problem: Peripheral Neuropathy (PN) is a series of disorders resulting from damage to the peripheral somatosensory nervous system resulting from lesion, injury, or disease. Debilitating symptoms of PN include numbness, tingling, and/or pain sensations such as allodynia (a normally non-painful stimulus causing pain) or hyperalgesia (an increased sensitivity to normally painful stimuli). PN can significantly affect quality of life. It is estimated that 1 in 15 Americans (i.e., 20.8M of 312M) suffer from PN. Currently, the most effective treatment of PN is pharmacological therapy. However, only 40-60% of patients achieve clinically meaningful relief, partially due to various types of neuropathy not being affected by ordinary analgesics. Many treatments cause debilitating side-effects due to their administration method (e.g., gastrointestinal) or the high levels of systemic uptake required to achieve effect. Alternative localized drug therapies do exist, but many have drawbacks to their administration methods. Needle injections cause acute pain, while topically-applied pain medications are limited by their molecular size since skin is virtually impermeable to molecules larger than 500 Daltons. A device is needed that can deliver PN medications to targeted areas through the skin, quickly and efficiently - regardless of molecular size. Hypothesis. LTA demonstrates feasibility of a hybrid US/iontophoresis topical PN treatment to efficiently deliver clinically-relevant dosages of gabapentin from 1% solution into porcine skin in vitro, leading to pre-clinical and clinical testing in Phase II. Aim 1 ? LTA US component permeabilizes skin ?5 minutes, and iontophoresis component accurately predicts skin permeabilization in vitro via secondary use as skin impedance measurement tool. Aim 2 ? Fifteen-minute operation of LTA in dual-mode delivers >25% of gabapentin dose into full- thickness porcine skin in vitro.