TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

Cell. 2020 Feb 17;:

Authors: Beaulieu-Laroche L, Christin M, Donoghue A, Agosti F, Yousefpour N, Petitjean H, Davidova A, Stanton C, Khan U, Dietz C, Faure E, Fatima T, MacPherson A, Mouchbahani-Constance S, Bisson DG, Haglund L, Ouellet JA, Stone LS, Samson J, Smith MJ, Ask K, Ribeiro-da-Silva A, Blunck R, Poole K, Bourinet E, Sharif-Naeini R

Abstract
Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.

PMID: 32084332 [PubMed - as supplied by publisher]

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Increased Hypothalamic Projections to the Lateral Hypothalamus and Responses to Leptin in Rat Neonates From High Fat Fed Mothers.

Increased Hypothalamic Projections to the Lateral Hypothalamus and Responses to Leptin in Rat Neonates From High Fat Fed Mothers.

Front Neurosci. 2019;13:1454

Authors: Kelley L, Verlezza S, Long H, Loka M, Walker CD

Abstract
The lateral hypothalamus (LHA) is a central hub in the regulation of food intake and metabolism, as it integrates homeostatic and hedonic circuits. During early development, maturing input to and output from the LHA might be particularly sensitive to environmental dietary changes. We examined the effects of a maternal high fat diet (HFD, 60% Kcal in fat) on the density of hypothalamic projections to the orexin (ORX-A) field of the LHA in 10 day-old (PND10) rat pups using retrograde labeling with fluorescent microspheres. We also compared responsiveness of phenotypically identified LHA neurons to leptin administration (3 mg/kg, bw) between pups from control (CD) or high fat (HFD) fed mothers on PND10 and 15-16, at the onset of independent feeding. HFD pups exhibited a higher density of LHA projections (p = 0.05) from the ventromedial hypothalamus (VMH) compared to CD pups and these originated from both SF-1 and BDNF-positive neurons in the VMH. Increased circulating leptin levels in HFD pups, particularly on PND15-16 was consistent with enhanced pSTAT3 responses to leptin in the orexin (ORX-A) field of the LHA, with some of the activated neurons expressing a GABA, but not CART phenotype. ORX-A neurons colocalizing with pERK were significantly higher in PND15-16 HFD pups compared to CD pups, and leptin-induced increase in pERK signaling was only observed in CD pups. There was no significant effect of leptin on pERK in HFD pups. These results suggest that perinatal maternal high fat feeding increases hypothalamic projections to the ORX-A field of the LHA, increases basal activation of ORX-A neurons and direct responsiveness of LHA neurons to leptin. Since these various LHA neuronal populations project quite heavily to Dopamine (DA) neurons in the ventral tegmental area, they might participate in the early dietary programming of mesocorticolimbic reward circuits and food intake.

PMID: 32082105 [PubMed]

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Long-term discourse outcomes and their relationship to white matter damage in moderate to severe adulthood traumatic brain injury.

Long-term discourse outcomes and their relationship to white matter damage in moderate to severe adulthood traumatic brain injury.

Brain Lang. 2020 Feb 17;204:104769

Authors: Marcotte K, Sanchez E, Arbour C, Brambati SM, Bedetti C, Martineau S, Descoteaux M, Gosselin N

PMID: 32078946 [PubMed - as supplied by publisher]

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Preformed pediatric zirconia crown versus preformed pediatric metal crown: study protocol for a randomized clinical trial.

Preformed pediatric zirconia crown versus preformed pediatric metal crown: study protocol for a randomized clinical trial.

Trials. 2019 Aug 24;20(1):530

Authors: Lopez-Cazaux S, Aiem E, Velly AM, Muller-Bolla M

Abstract
BACKGROUND: Guidelines in pediatric restorative dentistry recommend the use of preformed pediatric stainless steel crowns (SSCs) in cases of severe tooth decay of at least two surfaces. This clinically effective and safe restorative option is frequently refused by parents for esthetic reasons; they prefer conventional restorations using esthetic filling materials (composites, glass ionomer) if lesion severity limited to two surfaces permits. Recently, manufacturers have proposed esthetic preformed pediatric zirconia crowns (ZCs) but these have been assessed in only two randomized clinical trials (RCT) with follow-ups of 6 and 12 months. Only one of these RCTs was carried out on primary molars to test ZCs (NuSmile ZR) without a groove in its inner surface. The primary objective of this proposed RCT is to assess the effectiveness of ZCs compared with SSCs. Our hypothesis is that the effectiveness of ZCs will be equivalent to that of SSCs.
METHODS: In this split-mouth, 2-year RCT, pairs of primary molars in 101 child participants will be randomized and restored with SSCs (ESPE, 3M) and ZCs (EZCrowns, Sprig Oral Health Technologies) characterized by grooves on their inner surface. Primary molars will first be allocated to SSCs, and 1 to 2 weeks later the other primary molar of the same pair will be restored by ZC. The primary outcome is the success defined by the "absence of major clinical and radiographic failure" (e.g., pain, pulp infection, dental abscess or periradicular pathology visible on radiographs). The secondary outcomes include the retention and fracture rates, the gingival condition, the wear of the antagonist of the treated teeth, as well as both parental and child satisfaction.
DISCUSSION: This study will investigate two types of preformed pediatric crowns for the management of severe decay on primary molars. The results may help practitioners choose the better therapeutic option and to explain to parents the advantages and disadvantages of these two therapies.
TRIAL REGISTRATION: NCT03296709 . Registered on  27 September 2017.

PMID: 31445509 [PubMed - indexed for MEDLINE]

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