Children’s vicarious ratings of social touch are tuned to the velocity but not the location of a caress

Affective sharing is a bottom-up process involving automatic processing of sensory inputs that facilitate vicarious experience of another’s emotional state. It is grounded directly in the prior experiences of the perceiver. In adults, vicarious ratings of affective touch match the known velocity tuning and hypothesised anatomical distribution of C-tactile afferents (CT), a subclass of C-fibre which respond preferentially to low force/velocity stroking touch, typically perceived as pleasant. Given the centrality of touch to early nurturing interactions, here we examined whether primary school aged children’s vicarious ratings of affective touch show the same anatomical and velocity specific patterns reported in adults. Forty-four children aged between 8 and 11 (mean age 9, 24 male) rated a sequence of video clips depicting one individual being touched by another on 5 different upper-body sites (palm, dorsal forearm, ventral forearm, upper-arm and back) at 3 different velocities (static, CT optimal, slow stroking and non-CT optimal, fast stroking). Immediately after viewing each clip, participants were asked to rate how pleasant they perceived the touch to be. While children rated the CT optimal velocity significantly higher than static or non-CT optimal touch, unlike adults their ratings did not vary across skin sites. This difference may reflect the fact children’s ratings are grounded in bottom-up affective resonance while adults also draw on top-down cognitive evaluation of the broader social context when rating the stimuli.

Examination of the contribution of Nav1.7 to axonal propagation in nociceptors

Nav1.7 is a promising drug target for the treatment of pain because individuals with Nav1.7 loss-of-function mutations are insensitive to pain and do not have other serious neurological deficits. However, current peripherally restricted Nav1.7 inhibitors have not performed well in clinical pain trials, which may reflect a lack of understanding of the function of Nav1.7 in the transmission of nociceptive information. Although numerous studies have reported that Nav1.7 has a moderate role in peripheral transduction, the precise contribution of Nav1.7 to axonal propagation in nociceptors is not clearly defined, particularly for afferents innervating deep structures.In this study, we examined the contribution of Nav1.7 to axonal propagation in nociceptors utilising sodium channel blockers in in vivo electrophysiological and calcium imaging recordings from L4 in the mouse. Using the sodium channel blocker TTX (1-10μM) to inhibit Nav1.7 and other TTX-S sodium channels along the sciatic nerve, we first showed that around 2/3rds of nociceptive neurons innervating the skin, but a lower proportion innervating the muscle (45%), are blocked by TTX. In contrast, nearly all large-sized A-fibre cutaneous afferents (95-100%) were blocked by axonal TTX. Characterisation of TTX resistant cutaneous nociceptors revealed that many were polymodal (57%) and capsaicin sensitive (57%).Next, we examined the role of Nav1.7 in axonal propagation in nociceptive neurons by applying the selective channel blocker PF-05198007 (300nM-1μM) to the sciatic nerve between stimulating and recording sites. 100-300nM PF-05198007 blocked propagation in 63% of C-fibre sensory neurons, whereas similar concentrations did not affect propagation in rapidly conducting A-fibre neurons. We conclude that Nav1.7 has an essential contribution to axonal propagation in only around 2/3rds of nociceptive C-fibre neurons, and a lower proportion (≤45%) of nociceptive neurons innervating muscle.

CCCP

This chapter is concerned with Crispin Wright’s critique, in his 2002 “The Conceivability of Naturalism,” of the well-known argument developed in Saul Kripke’s Naming and Necessity against the identity of pain with C-fibre firing. Kripke argued that if the identity held it would do so necessarily, so that the identity theorist would have the task of explaining away the apparent conceivability of pain without C-fibre firing and C-fibre firing without pain. Wright identified a principle underlying Kripke’s argument (the “Counter-Conceivability Principle,” to the effect that a clear and distinct conception of a situation is the best possible evidence of its possibility), and suggested that Kripke’s deployment of it against the identity theory resulted in failure. The present chapter raises some doubts about the details of Wright’s diagnosis of the flaw in Kripke’s argument, and makes a contribution of its own to our understanding of the aetiology of modal illusion.

Differentiation of the 50B11 dorsal root ganglion cells into NGF and GDNF responsive nociceptor subtypes

The embryonic rat dorsal root ganglion (DRG) neuron-derived 50B11 cell line is a promising sensory neuron model expressing markers characteristic of NGF and GDNF-dependent C-fibre nociceptors. Whether these cells have the capacity to develop into distinct nociceptive subtypes based on NGF- or GDNF-dependence has not been investigated. Here we show that by augmenting forskolin (FSK) and growth factor supplementation with NGF or GDNF, 50B11 cultures can be driven to acquire differential functional responses to common nociceptive agonists capsaicin and ATP respectively. In addition, to previous studies, we also demonstrate that a differentiated neuronal phenotype can be maintained for up to 7 days. Western blot analysis of nociceptive marker proteins further demonstrates that the 50B11 cells partially recapitulate the functional phenotypes of classical NGF-dependent (peptidergic) and GDNF-dependent (non-peptidergic) neuronal subtypes described in DRGs. Further, 50B11 cells differentiated with NGF/FSK, but not GDNF/FSK, show sensitization to acute prostaglandin E2 treatment. Finally, RNA-Seq analysis confirms that differentiation with NGF/FSK or GDNF/FSK produces two 50B11 cell subtypes with distinct transcriptome expression profiles. Gene ontology comparison of the two subtypes of differentiated 50B11 cells to rodent DRG neurons studies shows significant overlap in matching or partially matching categories. This transcriptomic analysis will aid future suitability assessment of the 50B11 cells as a high-throughput nociceptor model for a broad range of experimental applications. In conclusion, this study shows that the 50B11 cell line is capable of partially recapitulating features of two distinct types of embryonic NGF and GDNF-dependent nociceptor-like cells.

Mechanical behaviour of fire-exposed fibre-reinforced sustainable concrete

Purpose Present study focuses on scope of developing sustainable heat resistant concrete by adding steel fibre (Sf) and polypropylene fibre (PPf) along with partially replacement of ordinary portland cement (OPC) and natural fine aggregate with fly ash (FA) and granular blast furnace slag (GBFS). Replacement percentages of FA and GBFS were 40% and 50%, whereas Sf and PPf for fibre-added mixes were 1% by volume of concrete and 0.25% by weight of cement, respectively. Design/methodology/approach An experimental work had been carried out to make comparison between control mix (CM), fibre-added sustainable mix (SCMF) and fibre-added control mix (CMF) with reference to weight loss, mechanical strength (compressive, split and flexure) after exposed to room temperature (27°C) to 1000°C at the interval of 200°C for 4 h of heat curing followed by furnace cooling and then natural cooling. Furthermore, microstructural analysis was executed at 27°C, 400°C and 800°C, respectively. Findings Colour change and hair line cracks were started to appear at 600°C. Fibre-added control mix and sustainable mix did not exhibit any significant cracks as compared to control mix even at 1000°C. Major losses were occurred at temperature higher than 600°C, loss in compressive strength was about 70% in control mix, while 60% in fibre-added mixes. SCMF exhibited the highest retention of strength with respect to all cases of mechanical strength. Research limitations/implications Present study is based on the slow heating condition followed by longer duration of heat curing at target temperature. Practical implications Present work can be helpful for the design engineer for assessing the fire deterioration of concrete structure existing near the fire establishment such as furnace and ovens. Building fire (high temperature for short duration) might be the further scope of work. Originality/value Concept of incorporating pozzolanic binder and calcareous fine aggregate was adopted to take the advantage pozzolanacity and fire resistivity. To the best of author’s knowledge, there is a scope for fill the research gap in this area.