Peripheral nerve injuries (PNI) are common and often result in lifelong disability. The peripheral nervous system has an inherent ability to regenerate following injury, yet complete functional recovery is rare. Despite advances in the diagnosis and repair of PNIs, many patients suffer from chronic pain, and sensory and motor dysfunction. One promising surgical adjunct is the application of intraoperative electrical stimulation (ES) to peripheral nerves. ES acts through second messenger cyclic AMP to augment the intrinsic molecular pathways of regeneration. Decades of animal studies have demonstrated that 20 Hz ES delivered post-surgically accelerates axonal outgrowth and end organ reinnervation. This work has been translated clinically in a series of randomized clinical trials, which suggest that ES can be used as an efficacious therapy to improve patient outcomes following PNIs. The aim of this review is to discuss the cellular physiology and the limitations of regeneration after peripheral nerve injuries. The proposed mechanisms of ES protocols and how they facilitate nerve regeneration depending on timing of administration are outlined. Finally, future directions of research that may provide new perspectives on the optimal delivery of ES following PNI are discussed.

Primary tumors can communicate with the liver to establish a microenvironment that favors metastatic colonization prior to dissemination, forming what is termed the “pre-metastatic niche” (PMN). Through diverse signaling mechanisms, distant malignancies can both influence hepatic cells directly as well as recruit immune cells into the PMN. The result is a set of changes within the hepatic tissue that increase susceptibility of tumor cell invasion and outgrowth upon dissemination. Thus, the PMN offers a novel step in the traditional metastatic cascade that could offer opportunities for clinical intervention. The involved signaling molecules also offer promise as biomarkers. Ultimately, while the existence of the hepatic PMN is well-established, continued research effort and use of innovative models are required to reach a functional knowledge of PMN mechanisms that can be further targeted.