Antinociceptive Effects of an Anti-CGRP Antibody in Rat Models of Colon-Bladder Cross-Organ Sensitization.

Irritable bowel syndrome (IBS) and bladder pain syndrome/interstitial cystitis (BPS/IC) are comorbid visceral pain disorders seen commonly in women with unknown etiology and limited treatment options and can involve visceral organ cross-sensitization. Calcitonin gene-related peptide (CGRP) is a mediator of nociceptive processing and may serve as a target for therapy. In three rodent models, we employed a monoclonal anti-CGRP F(ab') to investigate the hypothesis that visceral organ cross-sensitization is mediated by abnormal CGRP signaling.

Inter-axonal molecular crosstalk via Lumican proteoglycan sculpts murine cervical corticospinal innervation by distinct subpopulations.

How CNS circuits sculpt their axonal arbors into spatially and functionally organized domains is not well understood. Segmental specificity of corticospinal connectivity is an exemplar for such regional specificity of many axon projections. Corticospinal neurons (CSN) innervate spinal and brainstem targets with segmental precision, controlling voluntary movement.

Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting.

The cerebral cortex executes highly skilled movement, necessitating that it connects accurately with specific brainstem and spinal motor circuitry. Corticospinal neurons (CSN) must correctly target specific spinal segments, but the basis for this targeting remains unknown. In the accompanying report, we show that segmentally distinct CSN subpopulations are molecularly distinct from early development, identifying candidate molecular controls over segmentally specific axon targeting.

Corticospinal neuron subpopulation-specific developmental genes prospectively indicate mature segmentally specific axon projection targeting.

For precise motor control, distinct subpopulations of corticospinal neurons (CSN) must extend axons to distinct spinal segments, from proximal targets in the brainstem and cervical cord to distal targets in thoracic and lumbar spinal segments. We find that developing CSN subpopulations exhibit striking axon targeting specificity in spinal white matter, which establishes the foundation for durable specificity of adult corticospinal circuitry. Employing developmental retrograde and anterograde labeling, and their distinct neocortical locations, we purified developing CSN subpopulations using fluorescence-activated cell sorting to identify genes differentially expressed between bulbar-cervical and thoracolumbar-projecting CSN subpopulations at critical developmental times.

A Monoclonal Anti-Calcitonin Gene-Related Peptide Antibody Decreases Stress-Induced Colonic Hypersensitivity.

Irritable bowel syndrome (IBS) is a brain-gut disorder characterized by abdominal pain and altered bowel habits. Although the etiology of IBS remains unclear, stress in adulthood or in early life has been shown to be a significant factor in the development of IBS symptomatology. Evidence suggests that aberrant calcitonin gene-related peptide (CGRP) signaling may be involved in afferent sensitization and visceral organ hypersensitivity.

Lmo4 establishes rostral motor cortex projection neuron subtype diversity.

The mammalian neocortex is parcellated into anatomically and functionally distinct areas. The establishment of area-specific neuronal diversity and circuit connectivity enables distinct neocortical regions to control diverse and specialized functional outputs, yet underlying molecular controls remain largely unknown. Here, we identify a central role for the transcriptional regulator Lim-only 4 (Lmo4) in establishing the diversity of neuronal subtypes within rostral mouse motor cortex, where projection neurons have particularly diverse and multi-projection connectivity compared with caudal motor cortex.

On the geometric formulation of Hamiltonian dynamics.

Under a proper assignment of a metric and a connection, the (classical) dynamical trajectories can be identified as geodesics of the underlying manifold. We show how these geometric structures can be derived; specifically, we construct them explicitly for configuration and phase spaces of Hamiltonian systems. We demonstrate how the correspondence between geometry and dynamics can be applied to study the conserved quantities of a dynamical system.

RORβ induces barrel-like neuronal clusters in the developing neocortex.

Neurons in layer IV of the rodent whisker somatosensory cortex are tangentially organized in periodic clusters called barrels, each of which is innervated by thalamocortical axons transmitting sensory information from a single principal whisker, together forming a somatotopic map of the whisker pad. Proper thalamocortical innervation is critical for barrel formation during development, but the molecular mechanisms controlling layer IV neuron clustering are unknown. Here, we investigate the role in this mapping of the nuclear orphan receptor RORβ, which is expressed in neurons in layer IV during corticogenesis.

Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development.

Molecular controls over the development of the exceptional neuronal subtype diversity of the cerebral cortex are now beginning to be identified. The initial subtype fate decision early in the life of a neuron, and the malleability of this fate when the balance of key postmitotic signals is modified, reveals not only that a neuron is deterministically set on a general developmental path at its birth, but also that this program must be precisely executed during postmitotic differentiation. Here, we show that callosal projection neurons (CPN) and subcerebral projection neurons (subcerebral PN) in layer V of the neocortex share aspects of molecular identity after their birth that are progressively resolved during differentiation.

Pre-steady-state decoding of the Bicoid morphogen gradient.

Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may precede the convergence of the gradient to its steady state.

Subarachnoid morphine and fentanyl for labor analgesia. Efficacy and adverse effects.

Background And Objectives: The study was designed to compare analgesic efficacy and associated adverse effects between a group of parturients receiving subarachnoid opioids via the combined spinal-epidural (CSE) technique with a group receiving epidural analgesia alone for labor.

Methods: The authors studied 59 healthy parturients admitted for labor and delivery. Group 1 consisted of 26 consecutive patients who received the CSE technique, initially receiving subarachnoid morphine sulfate 0.

Effects of propofol and thiopental on maternal and fetal cardiovascular and acid-base variables in the pregnant ewe.

Background: The effects of propofol on uterine blood flow are not understood well. This is a relatively new agent that is finding increased use for nonobstetric surgical procedures during pregnancy and induction of anesthesia for cesarean section.

Methods: The effects of induction and maintenance of anesthesia with propofol were studied on maternal and fetal cardiovascular and acid-base variables in a chronically instrumented pregnant sheep model.

Hydralazine does not restore uterine blood flow during cocaine-induced hypertension in the pregnant ewe.

Cocaine abuse is widespread, and its use by the parturient has potential significant adverse effects in both the mother and the newborn. This study was undertaken in gravid ewes to determine the effects of treatment of cocaine-induced hypertension with hydralazine (Apresoline) on the maternal and fetal cardiovascular systems, catecholamine response, blood gas and acid-base status, and uterine blood flow (UBF). Twenty-one experiments were performed in 15 chronically instrumented ewes near term gestation.

Maternal and neonatal effects of adding epidural sufentanil to 0.5% bupivacaine for cesarean delivery.

Study Objective: To determine the maternal and fetal effects of the addition of epidural sufentanil to 0.5% bupivacaine for cesarean delivery.

Design: Randomized, double-blind, prospective study.

Maternal anesthesia and the stressed fetus: effects of isoflurane on the asphyxiated fetal lamb.

The effects of maternal isoflurane-oxygen anesthesia (isoflurane, 1% inspired) were measured in eight pregnant ewes and their asphyxiated singleton fetuses. Stable fetal asphyxia, indicated by a stable fetal arterial pH of 7.1-7.

Measurement of post-operative pain and narcotic administration in infants using a new clinical scoring system.

We developed a clinical neurologic and behavioral scoring system composed of 10 items to measure the post-operative pain levels in infants: (1) sleep during preceeding hour, (2) facial expression of pain, (3) quality of cry, (4) spontaneous motor activity, (5) Spontaneous excitability, (6) flexion of fingers and toes, (7) sucking, (8) global evaluation of tone, (9) consolability and (10) sociability. Using this system, a group of infants ranging from one to seven months in age and undergoing minor surgical procedures was studied. The infants were randomly assigned to two groups: Group I received Fentanyl intravenously (3 micrograms/kg) prior to surgery, and Group II received a placebo.

Cerebral handicap in full-term neonates related to the mechanical forces of labour.

Sometimes the relationship between peripartum events and neonatal CNS injury is obvious: for example, following complete abruptio placentae or umbilical cord prolapse and occlusion with a delay of many minutes before delivery of the baby. These circumstances are, of course, rare in modern obstetrics. Usually, when a neonate develops neurological injury, a host of various potentially adverse peripartum factors are assumed to be the aetiology, but without definitive evidence.

Effect of halothane on regional cerebral blood flow and cerebral metabolic oxygen consumption in the fetal lamb in utero.

The effects of halothane on maternal and fetal hemodynamics, distribution of fetal cardiac output, regional cerebral blood flow, and fetal cerebral oxygen consumption were studied in the ewe (N = 9) using radionuclide-labeled microspheres. An adjustable uterine artery occluder was used to produce a controlled state of fetal asphyxia. Measurements were taken during three periods of study: 1) control, 2) asphyxia, and 3) asphyxia plus 15 min of 1% maternal halothane.