Gendered relations? Associations between Swedish parents, siblings, and adolescents' time spent sedentary and physically active.

Introduction: The family is assumed to be fundamental in youth socialization processes and development, connected to social and cultural practices such as healthy lifestyles and physical activity. However, gender patterns in physical activity among adolescents and the structural drivers of gender inequality (e.g., parentage and siblingship) are poorly understood. The aim of this study was to explore further how gender structures relate to adolescents' time spent being sedentary and physically active, using contemporary gender theory. Methods: This cross-sectional study involved 1,139 adolescents aged 13-14 and their parents, including 815 mothers and 572 fathers. Physical activity and time spent sedentary were assessed through accelerometry among adolescents and through a self-report questionnaire for parents validated against accelerometry. Results: The results showed significant relationships between mothers' moderate-to-vigorous physical activity (MVPA) and girls' MVPA on weekdays and weekends, and fathers' MVPA was significantly related to girls' MVPA on weekdays. Our results imply that the relationship between Swedish parents' and adolescent girls' physical activity in higher intensities are to some extent gendered practices. However, time spent sedentary does not seem to show any patterns of being performed according to binary ideas of gender. Further, our exploratory analyses suggest that these results somewhat intersect with parents' educational level and relate to intra-categorical aspects of doing gender. The results also indicate slight gendered patterns in the "doing" of brotherhood for time spent sedentary, however, for boys only on weekends. Discussion: The study contributes to the understanding of gender norms as constraints and enablers for adolescents' participation in physical activity. The results can spur public health and physical activity research to apply a contemporary gender theory approach, and to expand the research agenda connected to what relates to gender inequalities in physical activity practices.

Genuine Movement Learning Through a Deleuzian Approach.

The purpose of the article is to outline how Deleuzian concepts, notably the notions of apprenticeship in signs based on a pedagogy of the concept, can stimulate thinking and understanding of movement learning, and provide insights about pedagogical implications in various movement educational settings. Methodologically, the article falls somewhere in between theoretical exposition and presentation of original empirical research, i.e., a "theoreticoempirical" exposition. We borrowed some ideas formulated by Deleuze (and Guattari), which have been further developed by educational researchers, about "an apprenticeship in signs" based on "a pedagogy of the concept," to analyse situations where students explore new movements. We use material generated from pedagogical interventions comprising of exploration of kinescapes. In these interventions, school and university students are encouraged to explore, and learn, juggling, unicycling and dancing. Findings indicate how students pass through interpretative illusions until some of them grasp difference in itself in what could be called its immanent differentiation of the actual, i.e., they learn how to juggle, unicycle or dance. This is what we designate genuine learning. The triadic relation between concepts, percepts and affects offer us clues to what juggling, unicycling or dancing mean to learners (concepts), what learners pay attention to while practising (percepts), and what gets them moving (affects). Importantly, through viewing learning as an apprenticeship in signs, the Deleuzian approach reminds us that the triadic relation is open-ended, meaning that concepts, percepts and affects are never final but always a potential actualisation. Concepts, percepts and affects are constantly in the process of becoming. Since genuine learning is not about narrowing down how a movement should be executed and experienced, the task of a movement educator could, then, be to accompany learners in explorative pursuits. In this way, teachers can help learners escape preconceptions about movements (who can do what and when) and instead explore new movement opportunities.

Associations between the School Environment and Physical Activity Pattern during School Time in Swedish Adolescents.

Knowledge about associations between school-based initiatives and physical activity patterns is limited. The purpose of this paper was to examine associations between factors in the school environment, physical activity and sedentary time during school time. The cross-sectional study included 1139 adolescents aged 13-14 from 34 schools. Physical activity and sedentary time were measured using hip-worn accelerometers. Factors in the school environment included health policy, a mobile phone ban during breaks, organized physical activities during breaks and activity breaks during lessons reported by teachers. The frequency and duration of breaks and physical education (PE) lessons were collected from school schedules. The results showed significant associations between health policy (ß = 3.87, 95% confidence interval (CI): 2.37, 5.23), the mobile phone ban (ß = 2.51, 95% CI: 1.29, 3.94) and PE; total duration (ß = 0.08, 95% CI: 0.05, 0.11), average duration (ß = 0.08, 95% CI: 0.01, 0.13) and frequency (ß = 1.73, 95% CI: 0.50, 3.04) and moderate-vigorous physical activity. There were negative associations between health policy (ß = -6.41, 95% CI: -10.24, -2.67), the mobile phone ban (ß = -3.75, 95% CI: -7.25, -0.77) and PE; total duration (ß = -0.15, 95% CI: -0.23, -0.08) and average duration (ß = -0.14, 95% CI: -0.27, -0.03) and time spent sedentary. Adolescents attending schools with health policies, mobile phone bans and more time for PE showed higher levels of physical activity and lower sedentary time.

Characterization of a 7 kDa pollen allergen belonging to the gibberellin-regulated protein family from three Cupressaceae species.

BACKGROUND: Severe allergy to fruits mediated by a 7 kDa allergen belonging to the gibberellin-regulated protein (GRP) family is known to be associated with Cupressaceae pollinosis. OBJECTIVE: To identify and characterize Cupressaceae pollen allergens involved in GRP-related fruit allergy. METHODS: Pru p 7-related proteins from pollen of Cupressus sempervirens, Juniperus ashei and Cryptomeria japonica were identified using a rabbit anti-Pru p 7 antiserum, purified chromatographically and sequenced by mass spectrometry and bioinformatic comparisons. The C sempervirens protein was produced as a recombinant allergen in Pichia pastoris. IgE antibody binding to pollen GRP proteins was analysed in a peach allergic (n = 54) and a cypress pollen allergic (n = 88) patient population from southern France using ImmunoCAP. RESULTS: In each of the three Cupressaceae species studied, a 7 kDa pollen protein related to Pru p 7 was identified and found to comprise an amino acid sequence of 63 residues in length, 92%-98% identical to each other and 67%-68% identical to Pru p 7. The C sempervirens, J ashei and C japonica GRP allergens have been officially recognized by the WHO/IUIS Allergen Nomenclature Sub-Committee and named Cup s 7, Jun a 7 and Cry j 7, respectively. Recombinant Cup s 7 showed IgE antibody binding capacity comparable to that of the purified natural allergen. Among 51 peach allergic subjects sensitized to Pru p 7, substantially higher levels of IgE to Cup s 7 than to Pru p 7 were found. Further, the pollen protein was able to completely outcompete IgE binding to Pru p 7, while the reverse competition effect was modest, consistent with primary sensitization by the pollen allergen. CONCLUSION AND CLINICAL RELEVANCE: Pru p 7-related pollen allergens from three Cupressaceae species have been characterized and may become useful for the identification of pollinosis patients at risk of developing severe fruit allergy.

Educational challenges facing swedish physical education teaching in the 2020s / Desafios educacionais para o ensino da educação física sueca na década de 2020 / Desafíos educativos para la educación física sueca en 2020

Abstract: Many countries around the world have experienced neoliberal turns which strongly affected educational systems. In Sweden, for example, the social democratic Welfare State has taken a radical neoliberal turn since the 1990s. A number of school reforms have been carried out and they are described as the most extensive in a hundred years of public schooling. These changes have also affected the subject of Physical Education and Health (PEH). Growing research interest is one of those changes, and PEH has become one of the most explored areas in Swedish physical culture. This article points to some of the new research, identifying and formulating possible educational challenges facing teachers as we move into the 2020s. Central questions are: What characterizes teaching in PEH? What do students learn in the subject? Is there effective evaluation in Swedish PEH?

Resumo: Muitos países pelo mundo vivenciaram uma virada neoliberal que fortemente afetou seus sistemas educacionais. Na Suécia, por exemplo, o Estado de Bem-Estar social-democrata foi radicalmente transformado desde a década de 1990, tomando uma direção neoliberal. Numerosas reformas educacionais foram realizadas, sendo estas descritas como as mais extensas em 100 anos do ensino público. Essas mudanças também afetaram a disciplina Educação Física e Saúde (PEH). Há um crescente interesse acerca desse tema e a PEH se tornou uma das áreas mais exploradas da cultura de movimento sueca. Os objetivos deste artigo são indicar as pesquisas recentes, bem como identificar e formular possíveis mudanças educacionais que professores enfrentam hoje enquanto caminhamos em direção à década de 2020. As questões centrais são: o que caracteriza o ensino em PEH? O que os estudantes aprendem nessa matéria? Existe eficácia na avaliação da PEH sueca?

Resumen: Muchos países alrededor de mundo han experimentado un cambio neoliberal que ha afectado fuertemente sus sistemas educativos. En Suecia, por ejemplo, el Estado de Bienestar Socialdemócrata se ha transformado radicalmente, desde los años 90, en una dirección neoliberal. Se han llevado a cabo numerosas reformas escolares, descritas como las más extensas en 100 años de educación pública. Estos cambios también afectaron a la Educación Física y Salud (PEH). Hay un creciente interés en este tema y la PEH se ha convertido en una de las áreas más exploradas de la cultura de movimiento sueca. Los propósitos de este artículo son señalar investigaciones recientes, identificar y formular posibles cambios educativos que actualmente enfrentan los maestros, a medida que avanzamos hacia la década de 2020. Las preguntas centrales son: ¿qué caracteriza la enseñanza en PEH? ¿Qué aprenden los estudiantes en esta materia? ¿Hay efectividad en la evaluación de la PEH sueca?

Swedish primary healthcare nurses' perceptions of using digital eHealth services in support of patient self-management.

BACKGROUND: Nurses have expressed doubts about the ongoing digitalisation of Swedish primary health care. Given the potential role of eHealth in primary health care, including supporting interactive self-management for people with chronic conditions, it is important to highlight nurses' experiences. This study is part of a larger project aimed at implementing person-centred interactive self-management support (iSMS) in primary health care. AIM: The aim of this study was to describe Swedish primary healthcare nurses' perceptions of using digital eHealth systems and services to support patient self-management. METHODS: Focus group interviews were conducted with primary healthcare nurses (n = 20). The interview transcriptions were analysed using qualitative content analysis. RESULTS: Three themes emerged from the content analysis: caregiving in the midst of digital chaos; a lack of overview and control in daily work; and mixed feelings towards digitalisation. Each theme was subdivided into three subthemes. CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: The results of this study provide insight into a number of concerns that stand in the way of success when it comes to the implementation and use of digital technology. If nurses are to adapt to the new policies and practices that accompany the current digitalised development in Swedish primary health care, the concept of a nurse's traditional work role needs to be amended in terms of the scope of work tasks and established views of traditional nursing. The study also highlights the need for more research to enable eHealth systems/services to be designed to fulfil multiple requirements. The digitised systems should be a tool for achieving good quality self-management support as well as giving the primary healthcare nurses adequate resources to support patients' self-management while still maintaining the values associated with person-centred care.

Herbivore grazing-or trampling? Trampling effects by a large ungulate in cold high-latitude ecosystems.

Mammalian herbivores have important top-down effects on ecological processes and landscapes by generating vegetation changes through grazing and trampling. For free-ranging herbivores on large landscapes, trampling is an important ecological factor. However, whereas grazing is widely studied, low-intensity trampling is rarely studied and quantified. The cold-adapted northern tundra reindeer (Rangifer tarandus) is a wide-ranging keystone herbivore in large open alpine and Arctic ecosystems. Reindeer may largely subsist on different species of slow-growing ground lichens, particularly in winter. Lichen grows in dry, snow-poor habitats with frost. Their varying elasticity makes them suitable for studying trampling. In replicated factorial experiments, high-resolution 3D laser scanning was used to quantify lichen volume loss from trampling by a reindeer hoof. Losses were substantial, that is, about 0.3 dm3 per imprint in dry thick lichen, but depended on type of lichen mat and humidity. Immediate trampling volume loss was about twice as high in dry, compared to humid thin (2-3 cm), lichen mats and about three times as high in dry vs. humid thick (6-8 cm) lichen mats, There was no significant difference in volume loss between 100% and 50% wetted lichen. Regained volume with time was insignificant for dry lichen, whereas 50% humid lichen regained substantial volumes, and 100% humid lichen regained almost all lost volume, and mostly within 10-20 min. Reindeer trampling may have from near none to devastating effects on exposed lichen forage. During a normal week of foraging, daily moving 5 km across dry 6- to 8-cm-thick continuous lichen mats, one adult reindeer may trample a lichen volume corresponding to about a year's supply of lichen. However, the lichen humidity appears to be an important factor for trampling loss, in addition to the extent of reindeer movement.

Oral baclofen reduces visceral pain-related pseudo-affective responses to colorectal distension in rats: relation between plasma exposure and efficacy.

OBJECTIVE: We previously showed that activation of GABA(B) receptors by intravenous baclofen reduces pseudo-affective responses to colorectal distension in rats. Here we evaluate the potential clinical significance of these observations. MATERIAL AND METHODS: Clinically relevant colorectal distension protocols were used to assess the effects of oral baclofen on visceromotor and autonomic cardiovascular responses in conscious rats. Plasma levels of baclofen were monitored to provide clinical relevance to the doses used. Conscious female Sprague-Dawley rats were subjected to repeated noxious colorectal distension (12 × 80 mmHg), ascending-phasic colorectal distension (10-80 mmHg, 10 mmHg increments) or ramp colorectal distension (10 min ramp at 8 mmHg/min). Visceromotor and cardiovascular responses (mean arterial blood pressure and heart rate) were monitored. Pain-related response thresholds were assessed using ascending-phasic and ramp colorectal distension. RESULTS: Baclofen (1-10 µmol/kg, p.o.) reduced the visceromotor response to colorectal distension, reaching a 40% maximal inhibition (p < 0.05). The highest dose (10 µmol/kg, p.o.) also inhibited pain-related cardiovascular responses in telemetrized rats (50-55% reduction in colorectal distension-evoked hypertensive and tachycardic responses; p < 0.05). Similar thresholds for pain-related visceromotor responses were determined during ramp or ascending-phasic colorectal distension (34.1 ± 1.9 and 31.7 ± 3.2 mmHg, respectively). Baclofen (10 µmol/kg, p.o.) increased thresholds to 71.1 ± 3.7 and 77.5 ± 1.8 mmHg during ramp and ascending-phasic colorectal distension, respectively (p < 0.001). Plasma levels of baclofen were 3.3 ± 0.2 µmol/l at 90 min post-dosing, corresponding to the end of the colorectal distension procedure. CONCLUSIONS: Oral baclofen, at plasma levels similar to those reported safe and within a therapeutic range in humans, produced significant visceral anti-nociceptive effects in rats.

Mugwort-sensitized individuals from North Europe, South Europe and North America show different IgE reactivity patterns.

BACKGROUND: Sensitization to weed pollen allergens at the molecular level is not fully understood. We studied IgE reactivity to the major mugwort allergen Art v 1 in relation to allergens from other weed pollen and cross-reactive components in mugwort-sensitized subjects. METHODS: Art v 1 and Amb a 1 were affinity purified and coupled to experimental ImmunoCAP® tests. Samples from North Europe (n = 50), South Europe (n = 19) and North America (n = 41) were analyzed for IgE against mugwort pollen, weed allergen components, pan-allergens and cross-reactive carbohydrate determinants (CCDs). RESULTS: The prevalence of IgE reactivity (>0.35 kU(A)/l) to Art v 1 was significantly higher in samples from North Europe than in those from North America. IgE to Amb a 1 was more common in North America than in North and South Europe, while IgE to Par j 2 was common in South Europe, less common in North America, and absent in North Europe. IgE to Art v 3 in mugwort-allergic patients was more common in North Europe than in South Europe and North America, while IgE to Sal k 1 was similar between the areas. Subjects with an Art v 1/mugwort-specific IgE ratio <0.5 had more often IgE to Amb a 1, profilin, polcalcin and CCDs than subjects with a ratio >0.5. CONCLUSIONS: Mugwort-sensitized subjects have different IgE reactivity profiles to weed allergens, reflecting their exposure to various pollens. Subjects with a low ratio between the IgE levels to Art v 1 and mugwort have a diverse IgE reactivity profile, indicating a role for cross-reactive allergens in their mugwort sensitization.

Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.

The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.

Involvement of the transient receptor potential vanilloid 1 (TRPV1) in the development of acute visceral hyperalgesia during colorectal distension in rats.

Transient receptor potential vanilloid 1 (TRPV1) channels have been implicated in pain mechanisms and, particularly, in the development of hyperalgesia. We used selective TRPV1 antagonists (NGV-1, SB-750364 and JYL 1421) to assess the role of TRPV1 channels in repetitive noxious colorectal distension (CRD)-induced visceral pain responses in rats. Isobaric CRD (80 mmHg) induced a viscerosomatic response, indicative of visceral pain associated to the distension procedure. Repetition (12 consecutive distensions) of the CRD resulted in an increase in the response over time (119+/-23% increase at distension 12, P<0.05 vs response during the 1st distension) indicative of acute mechanical sensitization. NGV-1 (0.1, 0.3, 1 or 3 micromol/kg, i.v.) prevented in a dose-related manner the development of sensitization, without inducing hypoalgesic responses. SB-750364 (30 micromol/kg, i.v.) had a transitory effect, partially reducing the sensitization response, while JYL 1421 (4.7 micromol/kg, i.v.) was without effect. In the same conditions, the cannabinoid receptor 1 (CB(1)) agonist, WIN55,212-2 (0.1 micromol/kg) reduced pain responses leading to a hypoalgesic state. At 3 micromol/kg, NGV-1, did not affect the pressure-volume relationship during CRD, indicating that TRPV1 channels do not modulate colonic compliance. These observations suggest that TRPV1 channels are involved in the development of acute mechanical colonic hyperalgesia during repetitive noxious CRD in rats. Antagonism of TRPV1 channels might result in antihyperalgesic effects without hypoalgesic activity and might be beneficial in the treatment of visceral pain disorders, such as irritable bowel syndrome. These observations warrant the clinical assessment of TRPV1 antagonists for the treatment of visceral pain.

CB1 receptors mediate the analgesic effects of cannabinoids on colorectal distension-induced visceral pain in rodents.

Activation of cannabinoid receptors (CB(1), CB(2) and GPR(55)) produces analgesic effects in several experimental pain models, including visceral pain arising from the gastrointestinal tract. We assessed the role of CB(1), CB(2), and GPR(55) receptors and the endogenous cannabinoid system on basal pain responses and acute mechanical hyperalgesia during colorectal distension (CRD) in rodents. The effects of cannabinoid receptor agonists and antagonists on pain-related responses to CRD were assessed in rats and in wild-type and CB(1) receptor knock-out mice. The dual CB(1/2) agonist, WIN55,212-2, and the peripherally acting CB(1)-selective agonist, SAB-378, inhibited pain-related responses to repetitive noxious CRD (80 mmHg) in a dose-related manner in rats. The analgesic effects of WIN55,212-2 and SAB-378 were blocked by the selective CB(1) antagonist SR141716, but were not affected by the selective CB(2) antagonist SR144528. SR141716, per se, increased the responses to repetitive noxious CRD, indicative of hyperalgesia, and induced pain-related responses during non-noxious CRD (20 mmHg), indicative of allodynia. The cannabinoid receptor agonists anandamide, virodhamine and O-1602 had no effect. At analgesic doses, WIN55,212-2 did not affect colonic compliance. In accordance to the rat data, WIN55,212-2 produced analgesia, whereas SR141716 induced hyperalgesia, during noxious CRD (55 mmHg) in wild-type but not in CB(1)-knock-out mice. These data indicate that peripheral CB(1) receptors mediate the analgesic effects of cannabinoids on visceral pain from the gastrointestinal tract. The allodynic and hyperalgesic responses induced by SR141716 suggest the existence of an endogenous cannabinoid tone and the activation of CB(1) receptors during noxious CRD.

Prostatic kallikrein: a new major dog allergen.

BACKGROUND: Dog dander is an important cause of respiratory allergy, but the spectrum of known dog allergens appears incomplete. Two lipocalins, Can f 1 and Can f 2, and serum albumin, Can f 3, have been characterized in detail but do not fully account for the IgE antibody-binding activity of dog dander extract. Allergen activity has previously been detected in dog urine but not further characterized. OBJECTIVE: We sought to identify, characterize, and assess the importance of allergen components in dog urine. METHODS: Dog urine was fractionated by means of size exclusion chromatography and examined for IgE antibody binding. A protein present in one fraction displaying IgE antibody-binding activity was identified by means of N-terminal sequencing and mass spectrometry. A recombinant form of the protein was produced in Pichia pastoris. IgE antibody binding to dog allergen components among sera of 37 subjects with dog allergy was determined by means of ImmunoCAP analysis. RESULTS: An IgE antibody-binding protein was isolated from dog urine and identified as prostatic kallikrein. A closely related or identical protein was detected in dog dander. The recombinant prostatic kallikrein displayed immunologic and biochemical properties similar to those of the natural protein and bound IgE antibodies from 26 (70%) of 37 sera of subjects with dog allergy, 14 of which reacted to none of Can f 1, Can f 2, or Can f 3. The dog allergen identified here was found to cross-react with human prostate-specific antigen, a key culprit in IgE-mediated vaginal reactions to semen. CONCLUSION: Prostatic kallikrein is a new major dog allergen.

Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats.

Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V(3)) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V(3) signaling system in the development of stress-induced visceral hyperalgesia in rats. Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10-60 mmHg) was assessed before and after stress. Animals were treated daily with SSR149415 (0.3, 1, or 3 mg/kg ip 30 min before each WAS or sham WAS session), with a single dose of SSR149415 (1 mg/kg ip), or the selective corticotropin-releasing factor 1 (CRF(1)) antagonist DMP-696 (30 mg/kg po) before CRD at day 11. Effects of a single dose of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension. These data support a major role for V(3) receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V(3) pathway might represent an attractive alternative to the CRF/CRF(1) pathway for the treatment of chronic stress-related gastrointestinal disorders.

The GABA(B) receptor agonist, baclofen, and the positive allosteric modulator, CGP7930, inhibit visceral pain-related responses to colorectal distension in rats.

Activation of GABA(B) receptors by the selective agonist baclofen produces anti-nociceptive effects in animal models of somatic pain. The aim of the present study was to evaluate the effect of baclofen and the GABA(B) receptor positive allosteric modulator CGP7930 on pseudo-affective responses to colorectal distension in rats. Female Sprague-Dawley rats were subjected to repeated, noxious colorectal distension (CRD) (12 distensions at 80 mmHg, for 30 s with 5 min intervals). The visceromotor response (VMR) and cardiovascular responses (mean arterial blood pressure (ABP) and heart rate (HR)) to CRD were monitored in conscious, telemetrized animals. Baclofen (0.3-3 micromol/kg, i.v.) reduced the VMR to CRD dose-dependently, reaching a 61% maximal inhibition (p < 0.001). The highest doses of baclofen attenuated CRD-evoked increases in ABP by 17% (p > 0.05) and reduced the change in HR by 48% (p < 0.01). CGP7930 (3-30 micromol/kg, i.v.) reduced the VMR to CRD in a dose-dependent fashion with a maximal inhibition of 31% (p < 0.05). The highest dose of CGP7930 also attenuated the increase in ABP by 18% (p > 0.05) and inhibited the increase in HR by 24% (p < 0.05) associated with CRD. Neither baclofen nor CGP7930 affected colorectal compliance. The results suggest that activation of GABA(B) receptors produces anti-nociceptive effects in a rat model of mechanically induced visceral pain. While CGP7930 was less efficacious than baclofen overall, positive allosteric modulation of GABA(B) receptors may represent a valid approach in the treatment of visceral pain conditions, with the possibility of an improved safety profile compared to full agonism.

Oral clonidine inhibits visceral pain-related viscerosomatic and cardiovascular responses to colorectal distension in rats.

The alpha(2)-adrenoceptor agonist, clonidine, modulates colorectal sensorimotor functions in humans and, given intrathecally, has analgesic effects in the colorectal distension (CRD) model in rats. We tested the effects of systemic clonidine on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats using clinically relevant CRD protocols. The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in arterial blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD. Pressure-volume relationships during CRD served as a measure of colonic compliance. Clonidine (50-200 nmol/kg, p.o.) dose-dependently inhibited the viscerosomatic response to phasic, noxious CRD (12 distension at 80 mm Hg). At 200 nmol/kg clonidine also attenuated the increase in blood pressure (70+/-7% inhibition, P<0.05) and heart rate (67+/-16% inhibition, P<0.05) associated to noxious CRD. Similar effects were observed after i.v. administration. Likewise, clonidine (200 nmol/kg, p.o.) reduced the response to ascending phasic CRD (10-80 mm Hg) and significantly increased the threshold pressure for pain-related responses. Clonidine (50 or 150 nmol/kg, i.p.) did not affect the pressure-volume relationship during phasic CRD (2-20 mm Hg). These results show that systemic clonidine, at doses devoid of visible side effects, has analgesic effects in the CRD model of visceral pain in rats without affecting colonic compliance. These observations confirm the analgesic activity of systemic clonidine on visceral pain, support the translational value of the rat CRD model to humans and show that manometry is more sensitive than electromyography detecting pain-related responses.

Role of tachykinin NK(1) and NK(2) receptors in colonic sensitivity and stress-induced defecation in gerbils.

The pharmacology of tachykinin NK receptors varies greatly among species. The aim of the present study was to assess the role of NK(1) and NK(2) receptors in mediating colorectal distension-evoked nociception and psychological stress-induced defecation in gerbils, a species with human-like NK receptor pharmacology. The effects of the selective NK(1) and NK(2) receptor antagonists, aprepitant and saredutant, on acute (1 h) restraint stress-evoked defecation and plasma adenocorticotropin (ACTH) levels in gerbils were assessed. The effects of antagonists alone or in combination on colorectal distension-evoked visceral pain in conscious gerbils were evaluated using the visceromotor response as a surrogate marker of pain. Restraint stress increased fecal pellet output 2-3-fold and plasma ACTH levels 9-fold. Aprepitant inhibited the defecatory and endocrine responses to stress by 50%, while saredutant completely normalized the same parameters. Visceral pain responses during colorectal distension were attenuated by both compounds, but aprepitant (19+/-6% inhibition, P<0.01) was slightly more effective than saredutant (10+/-9% inhibition, P<0.05). A combination of both compounds resulted in an additive effect (30+/-10% inhibition, P<0.01). The results demonstrate that NK(1) and NK(2) receptors are involved in stress-related colonic motor alterations and visceral pain responses in gerbils and that combined antagonism provides enhanced inhibition of visceral pain responses. This suggests that for therapeutic use in for instance functional gastrointestinal disorders, dual NK(1)/NK(2) receptor antagonists may provide better clinical outcome than selective compounds.