Queme LF, Ross JL, Lu P, Hudgins RC, Jankowski MP. Dual Modulation of Nociception and Cardiovascular Reflexes during Peripheral Ischemia through P2Y1 Receptor-Dependent Sensitization of Muscle Afferents. J Neurosci. 2016 Jan 6;36(1):19-30.
Many chronic pain conditions that affect children have a musculoskeletal component. Such conditions include complex regional pain syndrome, sickle cell anemia, juvenile fibromyalgia, and Ehlers-Danlos Syndrome. Children with these conditions often have significant impairment of blood flow to muscles in affected regions. However, the link between musculoskeletal pain and altered cardiovascular responses has remained elusive. In this study, Michael Jankowski, PhD, and colleagues examine receptors on nerve fibers that innervate muscles, and find that one type of purinergic receptor, the P2Y1 receptor, may regulate both cardiovascular reflexes as well as the transduction of chemical signals related to muscle pain. This finding indicates that this receptor mechanism represents a new therapeutic target for the treatment of concurrent muscle pain and ischemia.
Osterop SF, Virtanen MA, Loepke JR, Joseph B, Loepke AW, Vutskits L. Developmental stage-dependent impact of midazolam on calbindin, calretinin and parvalbumin expression in the immature rat medial prefrontal cortex during the brain growth spurt. Int J Dev Neurosci. 2015 Oct;45:19-28.
Exposure of newborn infants to anesthetics during surgery is a source of major concern as such exposures may cause lasting neurocognitive alterations. Anesthetics have the potential to kill neurons in the brain or change their development. However, tracking down these effects has been difficult, potentially because neurons at different developmental stages may be differentially affected. For example, the GABAergic transmitter system undergoes dramatic changes through the course of development. Early in development, this system is excitatory, while later in development it becomes inhibitory. Here Andreas Loepke, MD, PhD, and colleagues show that one compound - midazolam - can have profound effects on the development of inhibitory interneurons depending on which stage of development when administered. Early exposure of rat pups to midazolam caused increased levels of markers associated with neuron shrinkage and death, as well as increased numbers of cells expressing proteins such as parvalbumen. Later exposure produced increases in cells expressing both parvalbumen and calretinin. Both of these proteins are important in the regulation of calcium signaling, and as such, could provide a substrate for altered action of inhibitory neurons, which in turn may contribute to anesthetic-induced neurocognitive changes.
Singh SP, LaSarge CL, An A, McAuliffe JJ, Danzer SC. Clonal Analysis of Newborn Hippocampal Dentate Granule Cell Proliferation and Development in Temporal Lobe Epilepsy. eNeuro. 2016 Jan 9;2(6).
A portion of our brain, the hippocampus, continues to grow new neurons throughout our life. However, during epilepsy, newborn cells in this region become abnormal with altered shapes or changes in the way that they move from one region of the hippocampus to the other. The origin of these abnormal cells has remained poorly characterized. Steve Danzer, PhD, and colleagues have determined that a small subset of progenitor cells produce the majority of granule cells that migrate to abnormal locations, while cells with abnormal shapes arise throughout the pool of progenitor cells. These findings indicate that distinct mechanisms associated with the different abnormalities underscore the need for multiple therapeutic targets.
Vaughn LM, DeJonckheere M, Pratap JN. Putting a face and context on pediatric surgery cancelations: The development of parent personas to guide equitable surgical care. J Child Health Care. 2016 Jun 9. pii: 1367493516645858.
Last minute cancellation of a child's surgery can represent a major barrier to health care and represents a substantial loss of expensive health care resources. Finding ways of preventing such cancellations relies heavily on the preemptive identification of families at risk for cancellation. However, these families are not at all homogenous. As such, different strategies need developed for families in different situations. Nick Pratap, MB BChir, MRCPCH, FRCA, and colleagues surveyed 21 parents of children at risk for last minute cancellation in order to define different categories (a.k.a. personas) of families that would require distinct interventions to minimize the risk of late cancellation. They defined 5 different personas ranging from parents with substantial hospital experience to those with limited hospital experience, family support, and transportation challenges. These personas guide contextualized development of interventions tailored to prototypical families as they prepare and attend for surgery.
Thienprayoon R, Marks E, Funes M, Martinez-Puente LM, Winick N, Lee SC. Perceptions of the Pediatric Hospice Experience among English- and Spanish-Speaking Families. J Palliat Med. 2016 Jan;19(1):30-41.
The death of a child from disease or developmental abnormality is always a tragedy, and, sadly, remains a reality despite tremendous advances in medicine. Pediatric hospice care provides a means for guiding the child and their family through the end-of-life. However, pediatric hospice care is vastly different from adult hospice care due to distinct needs of patients and their families. Unfortunately, little remains known about the parental perspectives of the benefits and disappointments of the hospice experience, and accordingly, how pediatric hospice care can be better optimized. Moreover, culturo-linguistic differences in the hospice experience remain unknown. To address these gaps in knowledge, Dr. Thienprayoon, MD, MSCS, and colleagues surveyed both English and Spanish speaking parents of children who had received hospice care. Parents in both groups described caregiver strain. English-speaking families were more likely to highlight concerns about finances and insurance loss, while Spanish-speaking families described the difficulty of bedside caregiving and geographic hardship. Uncontrolled pain and symptom management remains a significant challenge.