Labeling PIEZO2 activity in the peripheral nervous system.

Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force.

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs.

Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity.

Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca]) fluctuations.

The transcription factor GrlA is regulated by subcellular compartmentalization and activated in response to mechanical stimuli.

Enterohemorrhagic (EHEC) is a foodborne pathogen that colonizes the gastrointestinal tract and has evolved intricate mechanisms to sense and respond to the host environment. Upon the sensation of chemical and physical cues specific to the host's intestinal environment, locus of enterocyte effacement (LEE)-encoded virulence genes are activated and promote intestinal colonization. The LEE transcriptional activator GrlA mediates EHEC's response to mechanical cues characteristic of the intestinal niche, including adhesive force that results from bacterial adherence to epithelial cells and fluid shear that results from intestinal motility and transit.

Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling.

Background: Available treatments for neuropathic pain have modest efficacy and significant adverse effects, including abuse potential. Because oxidative stress is a key mechanistic node for neuropathic pain, the authors focused on the master regulator of the antioxidant response-nuclear factor erythroid 2-related factor 2 (NFE2L2; Nrf2)-as an alternative target for neuropathic pain. The authors tested whether dimethyl fumarate (U.

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury.

Chronic pain following spinal cord injury (SCI) is associated with electrical hyperactivity (spontaneous and evoked) in primary nociceptors. Cyclic adenosine monophosphate (cAMP) signaling is an important contributor to nociceptor excitability, and knockdown of the cAMP effector, exchange protein activated by cAMP (EPAC), has been shown to relieve pain-like responses in several chronic pain models. To examine potentially distinct roles of each EPAC isoform (EPAC1 and 2) in maintaining chronic pain, we used rat and mouse models of contusive spinal cord injury (SCI).

The zebrafish as a model for gastrointestinal tract-microbe interactions.

The zebrafish (Danio rerio) has become a widely used vertebrate model for bacterial, fungal, viral, and protozoan infections. Due to its genetic tractability, large clutch sizes, ease of manipulation, and optical transparency during early life stages, it is a particularly useful model to address questions about the cellular microbiology of host-microbe interactions. Although its use as a model for systemic infections, as well as infections localised to the hindbrain and swimbladder having been thoroughly reviewed, studies focusing on host-microbe interactions in the zebrafish gastrointestinal tract have been neglected.

Sham surgeries for central and peripheral neural injuries persistently enhance pain-avoidance behavior as revealed by an operant conflict test.

Studies using rodent models of neuropathic pain use sham surgery control procedures that cause deep tissue damage. Sham surgeries would thus be expected to induce potentially long-lasting postsurgical pain, but little evidence for such pain has been reported. Operant tests of voluntary behavior can reveal negative motivational and cognitive aspects of pain that may provide sensitive tools for detecting pain-related alterations.

A Model for Holistic Review in Graduate Admissions That Decouples the GRE from Race, Ethnicity, and Gender.

Graduate schools around the United States are working to improve access to science, technology, engineering, and mathematics (STEM) in a manner that reflects local and national demographics. The admissions process has been the focus of examination, as it is a potential bottleneck for entry into STEM. Standardized tests are widely used as part of the decision-making process; thus, we examined the Graduate Record Examination (GRE) in two models of applicant review: metrics-based applicant review and holistic applicant review to understand whether it affected applicant demographics at The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain.

Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors, but rodent models of pain-related OA have concentrated on allodynia rather than ongoing pain, and on OA generated in non-nociceptive Aβ fibers rather than C-fiber nociceptors. Little is known about how ongoing pain or nociceptor OA is generated. To define neurophysiological alterations underlying nociceptor OA, we have used isolated dorsal root ganglion neurons that continue to generate OA after removal from animals displaying ongoing pain.

Persistent pain after spinal cord injury is maintained by primary afferent activity.

Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.