Why do we hunger for touch? The impact of daily gentle touch stimulation on maternal-infant physiological and behavioral regulation and resilience.

We report the impact of a Gentle Touch Stimulation (GTS) program. Forty-three mothers provided daily 10-min GTS with C-tactile (CT) afferent optimal stroking touch, for 4 weeks to their 3-12 weeks old infants. CT-afferents are cutaneous unmyelinated, low-threshold mechanosensitive nerves hypothesized to underly the regulatory impact of affective touch. We compared physiological and behavioral responses during a no-touch-baseline (BL), static-touch-baseline (BL-T), intervention/control (GTS/CTRL), Still Face (SF) and Reunion (RU) condition for GTS-infants versus a control-group (CTRL) at the start (T1) and end of (T2) of the program. We collected mother-infant ECG, respiration, cortisol, video-recordings, and diary-reports. At T1, physiological arousal significantly increased during SF in both groups, that is, decreased respiratory sinus arrhythmia (RSA) and R-R interval (RRI). At T2, GTS-infants showed significantly increased RSA, RRI, decreased respiration during GTS, buffering SF-arousal and allowing complete recovery during RU; CTRL-infants showed higher SF-arousal and small recovery, under initial BL-levels. Maternal cardio-respiratory showed a metabolic investment during RU. Cortisol and behavioral analyses showed higher arousal in CTRL-infants than GTS-infants at T2. We suggest that the combination of phasic short-term and tonic long-term responses to CT-optimal stroking touch, delivered in a structured daily manner, contribute to the building of infant stress regulation and resilience.

Reportamos el impacto del programa de Estimulación Táctil Suave (GTS). Cuarenta y tres madres les dieron a sus infantes de 3-12 semanas 10 minutos de GTS con un toque táctil-C (CT) aferente óptimo de caricias por 4 semanas. Los aferentes CT son nervios cutáneos amielínicos mecano-sensibles de bajo impacto que según hipótesis rigen el impacto regulatorio del toque afectivo. Comparamos las respuestas fisiológicas y de comportamiento durante un momento de referencia no táctil (BL), un momento de referencia táctil estático (BL-T), intervención/control (GTS-CTRL), la Cara Seria (SF) y la condición de Reunión (RU) para infantes GTS versus un grupo de control (CTRL) al principio (T1) y al final (T2) del programa. Recogimos información ECG de madre-infante, respiración, cortisol, grabaciones en vídeo, y reportes de un diario. Al T1, la estimulación fisiológica significativamente aumentó durante SF en ambos grupos, v.g., una baja en la arritmia respiratoria paranasal (RSA) y el intervalo R-R (RRI). Al T2, los infantes GTS significativamente mostraron un aumento de RSA, RRI, una baja en la respiración durante GTS, amortiguando la estimulación SF y permitiendo un completo recobro durante RU; los infantes de CTRL mostraron una más alta estimulación SF y un pequeño recobro, bajo los niveles BL iniciales. El aspecto cardio-respiratorio materno mostró inversión metabólica durante RU. Los análisis de cortisol y de comportamiento mostraron más altas estimulaciones de infantes de CTRL que en infantes GTS al T2. Proponemos que la combinación de las respuestas fásicas a corto plazo y tónicas a largo plazo a las caricias táctiles óptimas CT, ofrecidas de una manera estructural diaria, contribuyen a moldear la regulación del estrés y capacidad de resistencia del infante.

Cet article fait état de l'impact du programme Stimulation Toucher en Douceur (an anglais Gentle Touch Stimulation, que nous abrégeons ici GTS). Quarante-trois mères ont procédé chaque jour à un GTS de 10 minutes avec un toucher par caresse optimale C-tactile (CT) afférent, pendant 4 semaines à leurs nourrissons de 3-12 semaines. Les afférents CD sont des nerfs cutanés amyéliniques, à faible seuil et mécano-sensibles, dont on pense qu'ils sous-tendent l'impact régulatoire du toucher affectif. Nous comparons les réponses physiologiques et les réponses comportementales durant la condition à un niveau de référence NR sans toucher, un niveau de référence toucher statique (NR-T), un contrôle/intervention (GTS/CTRL), Visage Impassible (Still Face, soit SF) et la Réunion (RU) pour les bébés GTS par rapport aux bébés du groupe de contrôle (CTRL) au commencement (T1) et à la fin (T2) du programme. Nous avons recueilli l'électrocardiogramme mère-bébé, la respiration, le niveau de cortisol et les rapports-journaux. Au T1 la stimulation physiologique a augmenté de façon importante durant le SF pour les deux groupes, c'est-à-dire une arythmie des sinus respiratoires (RSA) décrue et un intervalle R-R décru (RRI). Au T2 les bébés GTS ont fait preuve d'une RSA et d'un RRI bien plus élevés, une respiration décrue durant le GTS, un éveil SF tampon et ont fait preuve d'un rétablissement complet durant la RU. Les bébés contrôle ont fait preuve de plus d'éveil SF et d'un petit rétablissement, moins élevés que les niveaux BL initiaux. La cardio-respiration maternelle a fait preuve un investissement métabolique durant la RU. Les analyses de cortisol et les analyses comportementales ont montré un éveil plus élevé chez les bébés-CTRL que chez les bébés GTS au T2. Nous suggérons que la combinaison de réactions phasiques à court terme et de réponses toniques à long terme au toucher caresse CT-optimal, donné chaque jour de manière structurée, contribue à la construction de la régulation du stress du bébé et de sa résilience.

let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following injury.

Neuronal injury often leads to devastating consequences such as loss of senses or locomotion. Restoration of function after injury relies on whether the injured axons can find their target cells. Although fusion between injured proximal axon and distal fragment has been observed in many organisms, its functional significance is not clear. Here, using Caenorhabditis elegans mechanosensory neurons, we address this question. Using two femtosecond lasers simultaneously, we could scan and sever posterior lateral microtubule neurons [posterior lateral microtubules (PLMs)] on both sides of the worm. We showed that axotomy of both PLMs leads to a dramatic loss of posterior touch sensation. During the regenerative phase, only axons that fuse to their distal counterparts contribute to functional recovery. Loss of let-7 miRNA promotes functional restoration in both larval and adult stages. In the L4 stage, loss of let-7 increases fusion events by increasing the mRNA level of one of the cell-recognition molecules, CED-7. The ability to establish cytoplasmic continuity between the proximal and distal ends declines with age. Loss of let-7 overcomes this barrier by promoting axonal transport and enrichment of the EFF-1 fusogen at the growing tip of cut processes. Our data reveal the functional property of a regenerating neuron.

Gentle Touch and Sucrose for Pain Relief during Suctioning in Preterm Newborns-A Randomized Clinical Trial.

Pain management is challenging in neonatal care. We aimed to compare the effects of gentle touch and sucrose on pain relief during suctioning in premature newborns (PTNB). This crossover randomized clinical trial enrolled PTNBs with low birth weight, hemodynamically stable, and requiring suctioning during hospitalization in the neonatal intensive care unit. PTNBs underwent three different suctioning procedures. The first was performed without intervention (baseline). Right after, PTNBs were randomly allocated (sucrose and gentle touch or vice versa) to the next two suctioning procedures. Two validated scales assessed pain: the Neonatal Infant Pain Scale (NIPS) and the Premature Infant Pain Profile-Revised (PIPP-R). We evaluated 50 PTNBs (mean of 28 weeks) with a mean low birth weight of 1050 g; most were under continuous positive airway pressure 37 (74%) and mechanical ventilation 41 (82%). Gentle touch was efficacious for pain relief since NIPS (p = 0.010) compared to baseline. Sucrose was also effective in reducing pain NIPS and PIPP-R (p < 0.001). Although the two interventions reduced pain, no difference was observed between gentle touch and sucrose.

The perception of pain, discriminative touch and affective touch in patients suffering from Borderline Personality Disorder.

Borderline Personality Disorder (BPD) is often characterized by self-injurious behaviors, with one-half to two-third of these patients reporting hypalgesic or analgesic phenomena during self-harming. Research on pain perception in BPD suggested abnormal processing of nociception either within the sensory-discriminative and/or motivational-affective systems of pain. Nevertheless, it is still unclear whether pain insensitivity could be generalized to other somatosensory submodalities. To investigate this question, 30 BPD patients and 30 matched healthy controls were enrolled in the current study and underwent a somatosensory battery composed of well-established psychophysical test assessing all the principal submodalities of somatosensation, namely pain perception (i.e., warm, cold and mechanical), discriminative touch (i.e., tactile acuity and tactile sensitivity) as well as affective touch. Results showed abnormal warm detection threshold, warm pain threshold, mechanical pain perception, and tactile sensitivity in BPD patients, but no differences emerged neither for tactile acuity nor for cold pain thresholds, cold tolerance, or for affective touch perception. Findings point to a deficit in nociception, as well as in tactile sensitivity in BPD individuals, and were discussed in relation to BPD clinical features including self-injurious behaviors.

Strengths and weaknesses of affective touch studies over the lifetime: A systematic review.

C-Tactile (CT) fibers are activated by slow, caress-like stimulations, and convey a specific tactile processing of hedonic and interpersonal components, defined as affective touch. Given the beneficial effects deriving from affective tactile experiences in social interactions at all ages, a systematic review of experimental studies on affective touch perception across the lifespan was performed with the aims of 1) examining whether and how affective touch has been studied in a systematic manner throughout the lifespan; 2) verifying whether the pleasantness associated to affective stimulations is found during the entire lifespan. Empirical human studies on affective touch were searched in two databases (PubMed, PsychINFO) and 112 articles were retrieved. Results indicated that most of the studies recruited participants with a mean age ranging from 18 to 40 years, whereas other age ranges came out as under-represented or not represented at all. Despite high heterogeneity across studies, affective touch was considered as a pleasant experience across the lifetime, and it was associated to specific psychophysiological patterns in infants and adults.

Pleasantness ratings in response to affective touch across hairy and glabrous skin: A meta-analysis.

The processing of hedonic aspects of touch, namely affective touch, is associated with the activation of C-Tactile (CT) fibers. CTs were thought to be present only in hairy skin, with glabrous skin being often used as control site in affective touch studies. Nevertheless, several articles comparing pleasantness perception across hairy and glabrous skin reported no significant differences. Surprisingly, CT fibers have also been recently detected on the glabrous palm, further questioning whether affective touch perception across both hairy and glabrous skin is comparable. The present meta-analysis thus aimed to quantify pleasantness perception of affective tactile stimulations on both hairy and glabrous sites. Pooled effect sizes (Hedges' g) from 18 studies were analyzed using random effect models. No systematic preference towards affective stimulations on hairy or glabrous skin was observed. Moreover, studies were highly heterogeneous, suggesting high variance in the results of the retrieved articles. Results were not affected by publication bias nor by other moderators. Variables affecting affective touch perception on hairy and glabrous skin and methodological considerations were discussed.

Affective touch: A meta-analysis on sex differences.

The unmyelinated C-tactile afferents system holds a hedonic function in touch experiences, shaping social functioning in the so-called affective touch hypothesis. Despite the fact that females are recognized as more sensitive to discriminative aspects of touch and respond more positively to touch than men, sex differences in the perception of affective touch have not been extensively investigated. We aimed to fill this gap by meta-analyzing existing studies on this topic. Thirteen studies were eligible and pooled effect sizes (Hedges' g) were compared. Random effect models were used. Results, which are not influenced by publication bias, show that there is a sex asymmetry in the pleasantness perceived during an affective tactile stimulation, with females showing higher pleasantness ratings than males. The size of the association does not vary as a function of sex distribution, age and methodological quality. Hormonal as well as evolutionary differences related to the caregiving and nurturing function of females may explain sex differences in affective touch. Results are limited by the small number of studies included in the meta-analysis.

Pleasantness Only?

When gently stroked with velocities between 0.1 and 30 cm/s, participants typically rate velocities around 3 cm/s as most pleasant, and the ratings follow an inverted u-shape. This pleasantness curve correlates often, but not always, with the firing rate of unmyelinated C-tactile (CT) afferents, leading to the notion that CT afferents code for the hedonic or emotional aspect of gentle touch. However, there is also evidence that CT firing does not necessarily equal pleasantness, and the range of attributes that CT afferents code for is not known. Here, participants were stroked with different velocities assumed to activate CT afferents to a different extent while they rated the touch on several sensory and emotional attributes. We expected an inverted u-shaped rating curve for pleasantness and other emotional attributes, but not for sensory attributes. Inverted u-shaped rating patterns were found for the emotional attributes "pleasant" and "not burdensome," but also for the sensory attribute "rough." CT-directed stimulation is thus not only experienced as hedonic. The sensations arising from CTs together with all other types of mechanoreceptors might be centrally integrated into a percept that represents those aspects which are most salient for the stimulation at hand.

The NompC channel regulates Nilaparvata lugens proprioception and gentle-touch response.

NompC channel is a member of the transient receptor potential (TRP) ion channel superfamily. It can regulate gentle-touch, locomotion, hearing and food texture detection in Drosophila. We cloned the NompC gene of Nilaparvata lugens (NlNompC). The full length NlNompC possessed similar structure as DmNompC, which belongs to TRPN subfamily. The expression pattern analysis of different developmental stages and body parts showed that the transcription of NlNompC was more abundant in adult stage and in the abdomen. Injection of double-stranded RNA (dsRNA) of NlNompC in the third-instar nymphs successfully knocked down the target gene with 75% suppression. At nine days after injection, the survival rate of dsRNA injected nymphs was as low as 9.84%. Behavioral observation revealed that the locomotion of the dsRNA injected nymphs was defective with much less movement compared to the negative control. Feeding and honeydew excretion of the dsRNA injected insects also decreased significantly. These results suggested that NlNompC is a classical mechanotransduction channel that plays important roles in proprioception and locomotion, and is essential for the survival of N. lugens. The results also contribute to the understanding of how TRP channels regulate proprioception.

Behavioral Mechanisms That Depend on Dopamine and Serotonin in Caenorhabditis elegans Interact With the Antipsychotics Risperidone and Aripiprazole.

The neurotransmitters dopamine and serotonin participate in specific behavioral neuromuscular mechanisms in the nematode Caenorhabditis elegans. Dopamine is involved in the gentle touch response and serotonin in the pharyngeal pumping rate. In its genome, the worm presents genes encoding dopamine and serotonin receptors orthologous to those of human genes. Risperidone and aripiprazole are a class of drugs known as atypical antipsychotics commonly used to treat schizophrenia, bipolar disorder, and irritability associated with autism. Risperidone is an antagonist of the dopamine D2 and serotonin 5-HT2A receptors. Aripiprazole functions as a partial agonist of the dopamine D2 receptor and as a partial agonist and antagonist of 5-HT1A and 5-HT2A serotonin receptors, respectively. Our results show that risperidone and aripiprazole alter the touch response and pharyngeal pumping in wild-type worm animals. Furthermore, in the presence of the drugs, both behaviors change to varying degrees in dopamine (dop-1, dop-2, and dop-3), serotonin (ser-1), and tyramine (ser-2) receptor-deficient mutants. This variation in response reveals specific targets for these antipsychotics in the nematode. Interestingly, their effect on behavior persisted to some extent in successive generations, indicating that they might induce epigenetic changes throughout development. Sodium butyrate, a histone deacetylase inhibitor, eliminated the consecutive generation effect of both drugs. In addition, these transgenerational effects were also abolished after the dauer stage. These observations suggest that risperidone and aripiprazole, in addition to interacting with specific receptors impairing the function of the nervous system of the nematode, may lead to the deposition of long-lasting epigenetic marks.

Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits?

Current research indicates that the causes of autism spectrum disorders (ASDs) are multifactorial and include both genetic and environmental factors. To date, several works have associated ASDs with mutations in genes that encode proteins involved in neuronal synapses; however other factors and the way they can interact with the development of the nervous system remain largely unknown. Some studies have established a direct relationship between risk for ASDs and the exposure of the fetus to high testosterone levels during the prenatal stage. In this work, in order to explain possible mechanisms by which this androgenic hormone may interact with the nervous system, C. elegans was used as an experimental model. We observed that testosterone was able to alter the behavioral pattern of the worm, including the gentle touch response and the pharyngeal pumping rate. This impairment of the behavior was abolished using specific RNAi against genes orthologous to the human androgen receptor gene. The effect of testosterone was eliminated in the nhr-69 (ok1926) deficient mutant, a putative ortholog of human AR gene, suggesting that this gene encodes a receptor able to interact with the hormone. On the other hand the testosterone effect remained in the gentle touch response during four generations in the absence of the hormone, indicating that some epigenetic mechanisms could be involved. Sodium butyrate, a histone deacetylase inhibitor, was able to abolish the effect of testosterone. In addition, the lasting effect of testosterone was eliminated after the dauer stage. These results suggest that testosterone may impair the nervous system function generating transgenerational epigenetic marks in the genome. This work may provide new paradigms for understanding biological mechanisms involved in ASDs traits.