Persistent changes in the dorsal root ganglion nociceptor translatome governs hyperalgesic priming in mice: roles of GPR88 and Meteorin.

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs because of reorganization of translation of mRNA in nociceptors.

Concentration dependent effects of human Cometin on spiral ganglion neuron survival and neurite outgrowth.

Introduction: Neurotrophic factors are widely known for their protective effect on spiral ganglion neurons (SGN) and the protection of these neurons is of great importance to optimize Cochlear Implants, which directly stimulate SGN in deaf patients. Previous studies have identified Cometin - also known as Meteroin-like - to be neuroprotective and beneficial for metabolic disorders. The aim of our study was to investigate the effects of different concentrations of recombinant human Cometin (hCometin) on SGN in regard to neuroprotection and neurite outgrowth and to evaluate its neurite guidance potential using a neurite outgrowth chamber.

Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors.

A novel reuptake inhibitor, IP2015, induces erection by increasing central dopamine and peripheral nitric oxide release.

Background And Purpose: An estimated 40% of patients with erectile dysfunction have a poor prognosis for improvement with currently available treatments. The present study investigated whether a newly developed monoamine transport inhibitor, IP2015, improves erectile function.

Experimental Approach: We investigated the effects of IP2015 on monoamine uptake and binding, erectile function in rats and diabetic mice and the effect on corpus cavernosum contractility.

Finding new analgesics: Computational pharmacology faces drug discovery challenges.

Despite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation.