NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.

Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells - monocytes, macrophages, and neutrophils - were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.

Introduction to a Twin Dual-Axis Robotic Platform for Studies of Lower Limb Biomechanics.

This paper presents a twin dual-axis robotic platform system which is designed for the characterization of postural balance under various environmental conditions and quantification of bilateral ankle mechanics in 2 degrees-of-freedom (DOF) during standing and walking. Methods: Validation experiments were conducted to evaluate performance of the system: 1) to apply accurate position perturbations under different loading conditions; 2) to simulate a range of stiffness-defined mechanical environments; and 3) to reliably quantify the joint impedance of mechanical systems. In addition, several human experiments were performed to demonstrate the system's applicability for various lower limb biomechanics studies. The first two experiments quantified postural balance on a compliance-controlled surface (passive perturbations) and under oscillatory perturbations with various frequencies and amplitudes (active perturbations). The second two experiments quantified bilateral ankle mechanics, specifically, ankle impedance in 2-DOF during standing and walking. The validation experiments showed high accuracy of the platform system to apply position perturbations, simulate a range of mechanical environments, and quantify the joint impedance. Results of the human experiments further demonstrated that the platform system is sensitive enough to detect differences in postural balance control under challenging environmental conditions as well as bilateral differences in 2-DOF ankle mechanics. This robotic platform system will allow us to better understand lower limb biomechanics during functional tasks, while also providing invaluable knowledge for the design and control of many robotic systems including robotic exoskeletons, prostheses and robot-assisted balance training programs. Clinical and Translational Impact Statement- Our robotic platform system serves as a tool to better understand the biomechanics of both healthy and neurologically impaired individuals and to develop assistive robotics and rehabilitation training programs using this information.