A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models

The neuron-restrictive silencing factor NRSF/REST binds to neuron-restrictive silencing elements in neuronal genes and recruits corepressors such as mSin3 to inhibit epigenetically neuronal gene expression. Because dysregulation of NRSF/REST is related to neuropathic pain, here, we have designed compounds to target neuropathic pain based on the mSin3-binding helix structure of NRSF/REST and examined their ability to bind to mSin3 by NMR. One compound, mS-11, binds strongly to mSin3 with a binding mode similar to that of NRSF/REST. In a mouse model of neuropathic pain, mS-11 was found to ameliorate abnormal pain behavior and to reverse lost peripheral morphine analgesia. Furthermore, even in the less well epigenetically defined case of fibromyalgia, mS-11 ameliorated symptoms in a mouse model, suggesting that fibromyalgia is related to the dysfunction of NRSF/REST. Taken together, these findings show that the chemically optimized mimetic mS-11 can inhibit mSin3-NRSF/REST binding and successfully reverse lost peripheral and central morphine analgesia in mouse models of pain.     

Random Encounter and Staying Time Model Testing with Human Volunteers

Ecology and management programs designed to track population trends over time increasingly are using passive monitoring methods to estimate terrestrial mammal densities. Researchers use motion-sensing cameras in mammal studies because they are cost-effective and advances in statistical methods incorporate motion-sensing camera data to estimate mammal densities. Density estimation involving unmarked individuals, however, remains challenging and empirical tests of statistical models are relatively rare. We tested the random encounter and staying time model (REST), a new means of estimating the density of an unmarked population, using human volunteers and simulated camera surveys. The REST method produced unbiased estimates of density, regardless of changes in human abundance, movement rates, home range sizes, or simulated camera effort. These advances in statistical methods when applied to motion-sensing camera data provide innovative avenues of large-mammal monitoring that have the potential to be applied to a broad spectrum of conservation and management studies, provided assumptions for the REST method are rigorously tested and met. © 2020 The Wildlife Society.