Experience-dependent structural changes in the developing brain are fundamental for proper neural circuit formation. Here, we show that during the development of the sensory cortex, dendritic field orientation is controlled by the BTB/POZ domain-containing 3 (BTBD3). In developing mouse somatosensory cortex, endogenous Btbd3 translocated to the cell nucleus in response to neuronal activity and oriented primary dendrites toward active axons in the barrel hollow. Btbd3 also directed dendrites toward active axon terminals when ectopically expressed in mouse visual cortex or normally expressed in ferret visual cortex. BTBD3 regulation of dendrite orientation is conserved across species and cortical areas and shows how high-acuity sensory function may be achieved by the tuning of subcellular polarity to sources of high sensory activity.

In both acute and chronic pain conditions, women tend to be more sensitive than men. This sex difference may be regulated by estrogens, such as estradiol, that are synthesized in the spinal cord and brainstem and act locally to influence pain processing. To identify a potential cellular source of local estrogen, here we examined the expression of aromatase, the enzyme that catalyzes the conversion of testosterone to estradiol. Our studies focused on primary afferent neurons and on their central targets in the spinal cord and medulla as well as in the nucleus of the solitary tract, the target of nodose ganglion-derived visceral afferents. Immunohistochemical staining in an aromatase reporter mouse revealed that many neurons in laminae I and V of the spinal cord dorsal horn and caudal spinal trigeminal nucleus and in the nucleus of the solitary tract express aromatase. The great majority of these cells also express inhibitory interneuron markers. We did not find sex differences in aromatase expression and neither the pattern nor the number of neurons changed in a sciatic nerve transection model of neuropathic pain or in the Complete Freund’s adjuvant model of inflammatory pain. A few aromatase neurons express Fos after cheek injection of capsaicin, formalin, or chloroquine. In total, given their location, these aromatase neurons are poised to engage nociceptive circuits, whether it is through local estrogen synthesis or inhibitory neurotransmitter release.

Estrogens are presumed to underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Although previous studies revealed populations of estrogen receptor-expressing neurons in primary afferents and in superficial dorsal horn neurons, there is little to no information as to the contribution of these neurons to the generation of acute and chronic pain. Here we molecularly characterized neurons in the mouse superficial spinal cord dorsal horn that express estrogen receptor α (ERα) and explored the behavioral consequences of their ablation. We found that spinal ERα-positive neurons are largely excitatory interneurons and many coexpress substance P, a marker for a discrete subset of nociceptive, excitatory interneurons. After viral, caspase-mediated ablation of spinal ERαexpressing cells, we observed a significant decrease in the first phase of the formalin test, but in male mice only. ERα-expressing neuron-ablation also reduced pruritogen-induced scratching in both male and female mice. There were no ablation-related changes in mechanical or heat withdrawal thresholds or in capsaicin-induced nocifensive behavior.In chronic pain models, we found no change in Complete Freund's adjuvant-induced thermal or mechanical hypersensitivity, or in partial sciatic nerve injury-induced mechanical allodynia. We conclude that ERα labels a subpopulation of excitatory interneurons that are specifically involved in chemically evoked persistent pain and pruritogen-induced itch.

Context. The cytotoxic regimens used in the contemporary day chemotherapy unit are often complicated and present numerous opportunities for error, inadvertent misadventure in prescription orders and variations in drug administration. The introduction of pre-printed chemotherapy charts for each protocol was introduced to minimise incorrect or incomplete prescribing by medical staff. Objective. To assess the benefits of introducing pre-printed chemotherapy charts into a day chemotherapy unit. Method. Commonly used protocols in the unit were assessed and assembled into pre-printed chemotherapy charts. The doses and administration details of each protocol were reviewed by chemotherapy nursing staff, medical staff and the oncology pharmacist before the charts were finalised. Clinical interventions performed by the oncology pharmacist were recorded for 1 month prior and 1 month following the introduction of the pre-printed charts. Nursing and medical staff were surveyed on their level of satisfaction with the pre-printed chemotherapy charts. Results. Prior to the introduction of the pre-printed charts, 74% of chemotherapy charts were problematic requiring multiple pharmacy interventions per chart. After the introduction of the pre-printed charts, 43% of charts were problematic requiring an average of one pharmacy intervention per chart. Pharmacy interventions were significantly reduced, which has resulted in a significant reduction in workload for the oncology pharmacist. The medical and nursing staff strongly supported the introduction of the pre-printed charts. There has been a reduction in the variation of orders amongst medical officers, reduction in prescribing errors, decreased anxiety amongst staff and better work-flow in the Day Chemotherapy Unit. Conclusion. Pre-printed chemotherapy medication charts have promoted a more methodical approach to the prescribing and administration of chemotherapy, which has resulted in a more efficient day chemotherapy unit.

No abstract