Chronic pain and complex regional pain syndrome are associated with alterations to the intestinal microbiota in both humans and mice. An observational cross-sectional study.

Objective: This study aimed to evaluate pain metrics and gut microbiota differences from human subjects with complex regional pain syndrome (CRPS) compared to cohabitants (HHC) and non-cohabitating (biobank) controls. In addition, we aimed evaluate longitudinal changes of gut microbiota using a mouse model of acute and chronic CRPS.

Methods: In an observational, cross-sectional study, 25 patients with CRPS and 24 household controls (HHC) were recruited, completed pain questionnaires, and submitted stool samples.

Acoustomechanically activatable liposomes for ultrasonic drug uncaging.

Ultrasound-activatable drug-loaded nanocarriers enable noninvasive and spatiotemporally-precise on-demand drug delivery throughout the body. However, most systems for ultrasonic drug uncaging utilize cavitation or heating as the drug release mechanism and often incorporate relatively exotic excipients into the formulation that together limit the drug-loading potential, stability, and clinical translatability and applicability of these systems. Here we describe an alternate strategy for the design of such systems in which the acoustic impedance and osmolarity of the internal liquid phase of a drug-loaded particle is tuned to maximize ultrasound-induced drug release.

Sex-distinct microglial activation and myeloid cell infiltration in the spinal cord after painful peripheral injury.

Chronic pain is a common and often debilitating problem that affects 100 million Americans. A better understanding of pain's molecular mechanisms is necessary for developing safe and effective therapeutics. Microglial activation has been implicated as a mediator of chronic pain in numerous preclinical studies; unfortunately, translational efforts using known glial modulators have largely failed, perhaps at least in part due to poor specificity of the compounds pursued, or an incomplete understanding of microglial reactivity.

The Tibial Fracture-Pin Model: A Clinically Relevant Mouse Model of Orthopedic Injury.

The tibial fracture-pin model is a mouse model of orthopedic trauma and surgery that recapitulates the complex muscle, bone, nerve, and connective tissue damage that manifests with this type of injury in humans. This model was developed because previous models of orthopedic trauma did not include simultaneous injury to multiple tissue types (bone, muscle, nerves) and were not truly representative of human complex orthopedic trauma. The authors therefore modified previous models of orthopedic trauma and developed the tibial fracture-pin model.

Mechanical Conflict-Avoidance Assay to Measure Pain Behavior in Mice.

Pain comprises of both sensory (nociceptive) and affective (unpleasant) dimensions. In preclinical models, pain has traditionally been assessed using reflexive tests that allow inferences regarding pain's nociceptive component but provide little information about the affective or motivational component of pain. Developing tests that capture these components of pain are therefore translationally important.

Combined single-molecule fluorescence hybridization and immunohistochemistry analysis in intact murine dorsal root ganglia and sciatic nerve.

Single-molecule fluorescence hybridization (smFISH) allows spatial mapping of gene expression. This protocol presents advances in smFISH fidelity and flexibility in intact murine sensory nervous system tissue. An approach using RNAscope probes allows multiplexing, enhanced target specificity, and immunohistochemistry compatibility.