Investigating the Function of Adult DRG Neuron Axons Using an In Vitro Microfluidic Culture System

Abstract

A critical role of the peripheral axons of nociceptors of the dorsal root ganglion (DRG) is the conduction of all-or-nothing action potentials from peripheral nerve endings to the central nervous system for the perception of noxious stimuli. Plasticity along multiple sites along the pain axis has now been widely implicated in the maladaptive changes that occur in pathological pain states such as neuropathic and inflammatory pain. Notably, increasing evidence suggests that nociceptive axons actively participate through the local expression of ion channels, receptors, and signal transduction molecules through axonal mRNA translation machinery that is independent of the soma component. In this report, we explore the sensitization of sensory neurons through the treatment of compartmentalized axon-like structures spanning microchannels that have been treated with the cytokine IL-6 and, subsequently, capsaicin. These data demonstrate the utility of isolating DRG axon-like structures using microfluidic systems, laying the groundwork for constructing the complex in vitro models of cellular networks that are involved in pain signaling for targeted pharmacological and genetic perturbations.