Evaluation of Nanoparticles for the Treatment of Chronic Neuropathic Pain

Abstract

Pain is something that will affect every person at some point in his or her lifetime, and yet chronic severe pain remains an often-undertreated medical condition as the current treatment protocol remains largely unsuccessful in reliably and safely managing pain. Nanoparticles (NPs) have gained momentum as a promising platform for solving previously unsolved medical issues. This work aimed to investigate the usefulness of a NP platform for the selective targeting and treatment of chronic pain. By researching naturally occurring neurotransmitters in the human body that regulate the pain response in mature neurons, a NP formulation was designed. This system involved coating 120 nm silica NPs with glutamic acid through the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) – N-hydroxysuccinimide (NHS) coupling reaction. The success of this conjugation was evaluated through a variety of analytical techniques and assays. The interactions of these particles with three main receptors in mature neurons, the γ- aminobutyric acid (GABA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) receptors, were analyzed to better understand how this particle would affect the propagation of pain signals through the nervous system. Combined with simulations of neurotransmitter effects on the hippocampal region of the brain, these results were used to develop a set of recommendations for the future progression and direction of this project.