A Hairy End to a Chilling Event.

In the skin, sympathetic nerves, arrector pili muscles, and hair follicles form a tri-lineage unit to cause piloerection or goosebumps. In this issue of Cell, Schwartz et al. report that, beyond goosebumps, muscle-anchored nerves form "synapse-like" connections with hair follicle stem cells to promote hair regeneration in response to cold.

Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells.

Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.

Valence, sensations and appraisals co-occurring with feeling moved: evidence on kama muta theory from intra-individually cross-correlated time series.

Emotional experiences typically labelled "being moved" or "feeling touched" may belong to one universal emotion. This emotion, which has been labelled "kama muta", is hypothesised to have a positive valence, be elicited by sudden intensifications of social closeness, and be accompanied by warmth, goosebumps and tears. Initial evidence on correlations among the kama muta components has been collected with self-reports after or during the emotion. Continuous measures during the emotion seem particularly informative, but previous work allows only restricted inferences on intra-individual processes because time series were cross-correlated across samples. In the current studies, we instead use a within-subject design to replicate and extend prior work. We compute intra-individual cross-correlations between continuous self-reports on feeling moved and (1) positive and negative affect; (2) goosebumps and subjective warmth and (3) appraisals of closeness and morality. Results confirm the predictions of kama muta theory that feeling moved by intensified communal sharing cross-correlates with appraised closeness, positive affect, warmth and (less so) goosebumps, but not with negative affect. Contrary to predictions, appraised morality cross-correlated with feeling moved as much as appraised closeness did. We conclude that strong inferences on emotional processes are possible using continuous measures, replace earlier findings, and are largely in line with theorising.

Being moved by meaningfulness: appraisals of surpassing internal standards elicit being moved by relationships and achievements.

People can be moved and overwhelmed, a phenomenon typically accompanied by goose-bumps and tears. We argue that these feelings of being moved are not limited to situations that are appraised as pro-social but elicited when someone surpasses an internal standard. In line with these predictions, people were moved by relationships and success (Study 1), by reunion, separation, success and failure (Study 2) and by social, environmental and sports achievements (Study 3). In all three studies, the elicitation of these feelings was partially mediated by appraisals of surpassing social or achievement standards. In line with this, ratings of meaningfulness were closely associated with feelings of being moved and moving stimuli elicited behavioural intentions such as spending time with family and friends, helping others and/or achieving something in life. Thus, moving situations may remind us about what we perceive as meaningful and thereby help us to act accordingly.

Styling without shedding: Novel topical formula reduces hair shedding by contracting the arrector pili muscle.

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α1 adrenergic receptor agonist, can be used to contract the arrector pili muscle of the follicular unit; thus, increasing the force required to pluck hair and reducing shedding during brushing. While demonstrating efficacy, phenylephrine has several drawbacks when applied to the scalp, including the possibility cardiovascular events. We hypothesized that a high concentration of a weak α1 agonist would allow for: (a) rapid penetration through the stratum corneum eliciting a quick response; (b) a low probability of cardiac adverse events owing to the low receptor binding affinity; and (c) an efficacy of the weak α1 agonist similar to that of phenylephrine at the local site of application. Accordingly, we developed a novel topical solution, AB-102, containing a high concentration of a weak α1 agonist. Several studies were conducted to test the safety and efficacy of AB-102. In a dose escalating safety study, utilizing a wearable holter monitor, we observed no cardiac or hemodynamic adverse events. In addition, in a controlled efficacy study, AB-102 reduced the number of hairs shed during brushing by up to 77% (average of 38%).

Moment-to-moment changes in feeling moved match changes in closeness, tears, goosebumps, and warmth: time series analyses.

Feeling moved or touched can be accompanied by tears, goosebumps, and sensations of warmth in the centre of the chest. The experience has been described frequently, but psychological science knows little about it. We propose that labelling one's feeling as being moved or touched is a component of a social-relational emotion that we term kama muta (its Sanskrit label). We hypothesise that it is caused by appraising an intensification of communal sharing relations. Here, we test this by investigating people's moment-to-moment reports of feeling moved and touched while watching six short videos. We compare these to six other sets of participants' moment-to-moment responses watching the same videos: respectively, judgements of closeness (indexing communal sharing), reports of weeping, goosebumps, warmth in the centre of the chest, happiness, and sadness. Our eighth time series is expert ratings of communal sharing. Time series analyses show strong and consistent cross-correlations of feeling moved and touched and closeness with each other and with each of the three physiological variables and expert-rated communal sharing - but distinctiveness from happiness and sadness. These results support our model.

α1 -AR agonist induced piloerection protects against the development of traction alopecia.

Traction alopecia is hair loss that occurs after persistent pulling (e.g., during cosmetic procedures) on the roots of hair over time. Unlike plucking, which is painful, persistent pulling may go unnoticed until a patient presents with either bald spots or diffuse telogen shedding. Each hair follicle in the scalp contains an arrector pili muscle that, when contracted, erects the hair. The smooth muscle in the arrector pili expresses α1 adrenergic receptors (α1 -AR). As such, we hypothesized that contraction of the arrector pili muscle via an α1 -AR agonist would increase the threshold of force required to pluck hair during cosmetic procedures. Female subjects, ages 18-40, were recruited to study the effect of topically applied phenylephrine, a selective α1 -AR agonist, on epilation force and hair shedding during cosmetic procedures. In our blinded study, 80% of subjects demonstrated reduced shedding on days using phenylephrine compared to days using a placebo solution. The average reduction in hair loss was approximately 42%. In addition, the force threshold required for epilation increased by approximately 172% following topical phenylephrine application. To our knowledge this is the first study demonstrating the utility of α1 -AR agonists in the treatment of traction alopecia and hair shedding during cosmetic procedures.

Sisters who developed piloerection after administration of milnacipran.

OBJECTIVE: We previously reported the first case of piloerection in a patient receiving milnacipran hydrochloride (MLP). Here, we now present a second case of MLP-induced piloerection. We discuss this effect in terms of α1-adrenoceptor occupancy. CASE SUMMARY: After the first case of MLP-induced piloerection, we monitored occurrence of piloerection in our patients taking MLP. In response to our interview, a 43-year-old woman who had been prescribed MLP by a psychiatrist for depression mentioned that piloerection occurred frequently all over her body, starting soon after initiation of MLP administration (50 mg/day). Although she was concerned at the time, she assumed it might be related to her depression or to coldness in winter. She also mentioned that the incidence of piloerection increased with MLP dose escalation. The piloerection disappeared after several months. Interestingly, the previous patient and the current patient are biological sisters. DISCUSSION: Changes in α1-adrenoceptor occupancy by endogenous norepinephrine (as an index of the risk of piloerection) in the presence of MLP were estimated. The occupancy values increased with MLP dose escalation, in accordance with the patient's report of the phenomenon. other concomitant drugs, such as nortriptyline, had little effect. Since the two patients were sisters, genetic factors might influence the risk of piloerection. CONCLUSION: The incidence of piloerection appeared to increase with MLP dose escalation in this patient, who was the biological sister of the previously reported patient. Clinicians should recognize the possibility of MLP-induced piloerection in view of its potential impact on patients' quality of life and on drug compliance.

'Goose bumps' as presenting feature of intraventricular glioblastoma multiforme.

'Goose-bumps' seizures are rare manifestations of epilepsy. They are rarely reported by patients and can be easily dismissed by clinicians. Clinically, it carries some diagnostic localising value especially with unilateral onset. In this report, we present a case of intraventricular glioblastoma multiforme with ipsilateral goose bumps and review the literature.

First chemical evaluation and toxicity of Casinga-cheirosa to Balb-c male mice.

Laetia suaveolens, known as "casinga-cheirosa", crude extract EB719 has previously shown cytotoxic activity against prostate cancer and squamous cell carcinoma. For the first time, seven molecules were isolated from its apolar-α-tocopherol (1) and sitosterol (2)-and polar-3-O-caffeoylquinic acid (3), 4-O-caffeoylquinic acid (4), 5-O-feruloylquinic acid (5), hyperoside (6), and isoquercitrin (7)-fractions. Acute toxicity was determined in a two-stage experiment: (1) a reduced number of Balb-c male mice received 5000 mg/kg of EB719 to allow evaluation of general activity and other 27 parameters, plus death, up to the establishment of non-lethal dose (NLD), as well as lethal dose 50% (LD50); (2) NLD was administered and diazepam introduced as reference drug. EB719 showed LD50=178.0 mg/kg, and NLD 156.3 mg/kg. In stage one EB719 did not influence general activity, but provoked impairment in grasp reflexes, tail squeeze and breathing; piloerection and cyanosis were increased. In stage two, alterations occurred in auricular reflex, piloerection and breathing after diazepam administration, but not in response to EB719. Intestinal hemorrhage caused by local bleeding was observed after necropsy, and may be the main cause of animals' death other than a systemic effect of the extract. Although the isolated compounds are biologically and pharmacologically active in both men and animal systems, it is premature to relate their occurrence in EB719 to the observed intestine hemorrhage in mice.

The role of piloerection in primate thermoregulation.

The insulating properties of the primate integument are influenced by many factors, including piloerection, which raises the hair and insulates the body by creating motionless air near the skin's surface. The involuntary muscles that control piloerection, the musculi arrectores pilorum (MAP), are mostly absent except on the tail in most strepsirhines, and are entirely absent in tarsiers and some lorisids. The absence of piloerection and the reduced effectiveness of pilary insulation in preventing heat loss affected the evolution of behavior and metabolic thermoregulation in these animals. In lemurs, this situation contributed to the use of positional and social behaviors such as sunning and huddling that help maintain thermal homeostasis during day-night and seasonal temperature cycles. It also contributed in many lemurs and lorises to the evolution of a wide variety of activity patterns and energy-conserving metabolic patterns such as cathemerality, daily torpor, and hibernation. The absence of functional MAP in strepsirhines and tarsiers implies the absence of effective piloerection in early primates, and the reacquisition of whole-body MAP in ancestral anthropoids prior to the separation of platyrrhine and catarrhine lineages. © 2013 S. Karger AG, Basel.

Pilomotor seizures: a video case report.

Piloerection is a rare ictal manifestation usually associated with temporal lobe epilepsy. We present video and electrographic documentation of pilomotor seizures in a 75-year-old man with left temporal lobe epilepsy and remote herpes zoster encephalitis. In general, piloerection is most often localised to the temporal lobe. Unilateral piloerection is usually associated with an ipsilateral ictal onset. Bilateral piloerection has a less certain lateralising value, although earlier reports suggest left hemispheric predominance [Published with videosequences].

The physiological study of emotional piloerection: A systematic review and guide for future research.

This paper provides an accessible review of the biological and psychological evidence to guide new and experienced researchers in the study of emotional piloerection in humans. A limited number of studies have attempted to examine the physiological and emotional correlates of piloerection in humans. However, no review has attempted to collate this evidence to guide the field as it moves forward. We first discuss the mechanisms and function of non-emotional and emotional piloerection in humans and animals. We discuss the biological foundations of piloerection as a means to understand the similarities and differences between emotional and non-emotional piloerection. We then present a systematic qualitative review (k = 24) in which we examine the physiological correlates of emotional piloerection. The analysis revealed that indices of sympathetic activation are abundant, suggesting emotional piloerection occurs with increased (phasic) skin conductance and heart rate. Measures of parasympathetic activation are lacking and no definite conclusions can be drawn. Additionally, several studies examined self-reported emotional correlates, and these correlates are discussed in light of several possible theoretical explanations for emotional piloerection. Finally, we provide an overview of the methodological possibilities available for the study of piloerection and we highlight some pressing questions researchers may wish to answer in future studies.

Piloerection is not a reliable physiological correlate of awe.

In scientific and popular literature, piloerection (e.g. goosebumps) is often claimed to accompany the experience of awe, though this correlation has not been tested empirically. Using two pre-registered and independently collected samples (N = 210), we examined the objective physiological occurrence of piloerection in response to awe-inducing stimuli. Stimuli were selected to satisfy three descriptors of awe, including perceptual vastness, virtual reality, and expectancy-violating events. The stimuli reliably elicited self-reported awe to a great extent, in line with previous research. However, awe-inducing stimuli were not associated with the objective occurrence of piloerection. While participants self-reported high levels of goosebumps and "the chills," there was no physical evidence of this response. These results suggest that piloerection is not reliably connected to the experience of awe-at least using stimuli known to elicit awe in an experimental setting.

Dissociation between neurovegetative signs and subjective symptoms in a case of idiopathic pilomotor seizures.

OBJECTIVE: Pilomotor seizure (PS) is a rare subtype of simple and complex partial seizures, often related to temporal lobe epilepsy and occasionally linked to alterations of amygdala. The physiologic role played by this latter region in the coordination of autonomic responses to fear-induced emotional changes raises the question as to whether the involvement of amygdala in PS might elicit a disconnection between subjective symptoms and neurovegetative signs. METHODS: We report a case of idiopathic bilateral PS studied with video electroencephalogram, polygraphic 24-hour Holter electroencephalogram, and magnetic resonance imaging, plus spectral functional magnetic resonance imaging, in which the seizures were associated with abrupt tachycardia occurring in a state of emotional neutrality, without either clouding or loss of consciousness. RESULTS: Electroencephalogram documented PS episodes occurring during waking, rapid eyes movements, and nonrapid eye movement sleep stages. Although no morphologic alteration was detected, spectral magnetic resonance imaging visualized alterations of the metabolic ratios of N-acetylaspartate and creatine-phosphocreatine in hippocampus and amygdala, whereas no apparent involvement of the temporal lobe was found. CONCLUSIONS: These findings suggest that the limited involvement of amygdala and hippocampus in PS triggers the repertoire of fear-related sympathetic responses uncoupled from alterations in emotional status. This phenomenon supports the possibility that autonomic responses involved in fear or extreme alertness follow a kind of "ethological" modularity.

[A study of skin deformation by optical coherent microscopy].

The deformation of rat skin in response to cooling and stimulation of nerve fibers innervating the muscles piloerectors and vasoconstrictors has been studied by optical coherent microscopy. It has been found that the deformation of the skin on cooling occurs due to the contraction of bundles of collagen fibers rather than smooth muscles of vessels and piloerectors.

Ictal piloerection is associated with high-grade glioma and autoimmune encephalitis-Results from a systematic review.

PURPOSE: To comprehensively analyze ictal piloerection (IP) in a large number of subjects. METHODS: We performed a systematic review on case report studies of patients diagnosed with IP (1929-2017) with additional cases included from the Department of Neurology of University of Pécs, the National Institute of Clinical Neurosciences, and Odense University Hospital. Each included case was characterized regarding patient history, IP seizure characteristics, diagnostic work-up, and therapy. Comparative analyses were also carried out based on sex and pathology. RESULTS: Altogether, 109 cases were included. We observed a strong male predominance (p < 0.001). The mean age at onset of epilepsy was 39.5 ± 20.7 years (median: 38, IQR:24-57). The seizure onset zone was temporal (p < 0.001), and was lateralized to the ipsilateral hemisphere in unilateral localization (p = 0.001). The seizure was accompanied by cold shiver in 53%, and by other autonomic symptoms in 47% of cases. In 53% of patients, IP never progressed into complex partial or generalized tonic-clonic seizure; 16% of the patients reported occasional, and 31% regular generalization. Seizure frequency was higher among females (median:25/day, IQR:3-60) than among males (median:3/day, IQR:1-11) (p = 0.017). The two most common underlying pathologies were limbic encephalitis (23%) and astrocytoma (23%, among them 64% WHO III-IV astrocytoma). CONCLUSION: IP was particularly associated with autoimmune encephalitis and high-grade glioma, suggesting IP's particular clinical importance in directing diagnostic work-up.

The effects of rewarding ventral tegmental area stimulation and environmental enrichment on lipopolysaccharide-induced sickness behavior and cytokine expression in female rats.

Responding for rewarding brain stimulation has been used to track hedonic status in animals. In addition to neurochemical alterations, stimulation of the lateral hypothalamus or ventral tegmentum has been shown to influence immunological processes, including elevation of peripheral natural killer cell activity. In the present study, we examined whether ventral tegmental area (VTA) stimulation or environmental enrichment altered the severity of lipopolysaccharide (LPS)-induced sickness behaviors and the provocation of cytokine expression induced by the endotoxin. Accordingly, rats received either trials of brain stimulation reward or exposure to an enriched environment and subsequently challenged with 150 ug/kg i.p. of LPS. Groups receiving LPS and saline injections without further manipulation were also included. Using the real-time RT-PCR and a multiplex bead assay, mRNA and protein levels for several cytokines and their receptors were determined to evaluate how these may vary as a consequence of reward. Both brain stimulation and environmental enrichment similarly diminished sickness behaviors associated with the endotoxin. Receptor gene levels were generally stable across groups. Levels of IL-6 within the VTA were increased in the group receiving LPS challenge alone and environmental enrichment was associated with modestly reduced IL-6 levels within this brain region. Taken together, these data suggest that rewarding brain stimulation and environmental enrichment buffer against malaise provoked by endotoxin challenge. Moreover, IL-6 expression within the VTA may influence the development of sickness behavior following inflammatory stimuli.