The role of interoception in learned visceral control

Research concerned with the psychology and physiology of interoceptive processes is reviewed with the purpose of evaluating theoretical formulations of learned visceral control. Basic animal research in interoception provides relevant information; however, much research dealing directly with interoception and learned control is inadequate due either to inappropriate measurement of interoceptive ability or to poor experimental design. The two primary theoretical orientations linking interoception and learned visceral control differ according to the role ascribed to external feedback; the first views feedback as an enhancement of interoceptive cues, the second as an enhancement of exteroceptive cues. These theories are discussed with regard to recent investigations of learned visceral control.     

The role of dorsal columns pathway in visceral pain

Traditionally, the dorsal column-medial lemniscus system has been viewed as a pathway not involved in pain perception. However, recent clinical and experimental studies have provided compelling evidence that implicates an important role of the dorsal column pathway in relaying visceral nociceptive information. Several clinical studies have shown that a small lesion that interrupts fibers of the dorsal columns (DC) that ascend close to the midline of the spinal cord significantly relieves pain and decreases analgesic requirements in patients suffering from cancer originating in visceral organs. Behavioral, electrophysiological and immunohistochemical methods used under experimental situations in animals showed that DC lesion lead to decreased activation of thalamic and gracile neurons by visceral stimuli, suppressed inhibition of exploratory activity induced by visceral noxious stimulation and prevented potentiation of visceromotor reflex evoked by colorectal distention under inflammatory conditions. Whereas the surgical lesion of the DC tract has proven to be clinically successful, a pharmacological approach would be a better strategy to block this pathway and thus to improve visceral pain conditions under less dramatic circumstances than cancer pain. Our finding that PSDC neurons start to express receptors for substance P after colon inflammation suggests new targets for the development of pharmacological strategies for the control of visceral pain.     

The role of TRPA1 in visceral inflammation and pain

Despite significant progress in our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses and the establishment of hypersensitivity. This review summarizes the current knowledge of the role of TRPA1 in sensory transduction, particularly in the context of visceral inflammation and pain in the gastrointestinal and urinary tracts.     

The sleep and the visceral function control

The review focuses on rapidly growing body of data indicating that disturbances of the natural sleep and sleep deprivation lead to various visceral disorders. The review mentions consequences of sleep disturbances on the gastro-intestinal system, cardio-vascular and respiratory, immune, endocrine and reproductive functions. In order to establish the functional link between the sleep and the visceral health it is proposed that during sleep the central nervous system including all cortical areas switches from the processing of the exteroceptive information to the processing of the interoceptive information. Review of the studies, which offer the direct confirmation of this hypothesis, is presented.     

The role of TRPA1 in visceral inflammation and pain

Despite significant progress in our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses and the establishment of hypersensitivity. This review summarizes the current knowledge of the role of TRPA1 in sensory transduction, particularly in the context of visceral inflammation and pain in the gastrointestinal and urinary tracts.     

The role of the visceral yolk sac in hyperglycemia-induced embryopathies in mouse embryos in vitro.

The adverse developmental effects of hyperglycemia to rodent embryos have been shown using whole embryo culture. Although, a mechanism by which hyperglycemia-induced effects occur is unknown, recent work has focused on the visceral yolk sac as a potential target tissue. Therefore, we have evaluated the developmental effects of hyperglycemia in early head fold stage mouse embryos in vitro and assessed the histiotrophic function of the visceral yolk sac. As has been previously shown in rodents, hyperglycemia produced neural tube closure defects in a concentration dependent manner at 33, 50, and 67 mM glucose using a 44 h exposure period. However, exposure times between 6 and 12 h were sufficient to alter embryonic development when the glucose concentration was 50 or 67 mM. In contrast, early somite stage embryos (4-6 somite stage) appear to be less sensitive to dysmorphogenesis and a 48 h exposure to 67 mM glucose but not 33 or 50 mM also produced neural tube defects. Hyperglycemia (67 mM) did not alter the uptake of 35S-methionine and 35S-cysteine-labeled hemoglobin (35S-Hb) in the visceral yolk sac (VYS) in early headfold staged embryos. However, the accumulation of 35S in the embryo was reduced by 16-18% at glucose concentrations of 50 or 67 mM during the last 12 h of a 44 h exposure period. No effect on VYS uptake or embryonic accumulation of 35S-labeled products was observed at shorter exposure periods (12-24 and 24-36 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of endocannabinoids in the hypothalamic regulation of visceral function

The hypothalamus plays an important role in the regulation of several visceral processes, including food intake, thermoregulation and control of anterior pituitary secretion.Endogenous cannabinoids and CB(1) cannabinoid receptors have been found in the hypothalamus. In the present review, we would like to clarify the role of the endocannabinoid system in the regulation of the above-mentioned visceral functions.There is historical support for the role of marihuana (i.e. exogenous cannabinoids) in the regulation of appetite. Endocannabinoids also stimulate food intake. Furthermore, the specific CB(1) receptor antagonist SR141716 reduces food intake. Leptin treatment decreases endocannabinoid levels in normal rats and ob/ob mice. These findings provide evidence for the role of the hypothalamic endocannabinoid system in food intake and appetite regulation.Cannabinoids can change body temperature in a dose-dependent manner. High doses cause hypothermia while low doses cause hyperthermia. Cannabinoid administration decreases heat production. It seems that the effects of can- nabinoids on thermoregulation is exerted by altering some neurochemical mediator effects at both the presynaptic and postsynaptic level.THC and endocannabinoids have mainly inhibitory effects on the regulation of reproduction. Administration of anandamide (AEA) decreases serum luteinizing hormone (LH) and prolactin (PRL) levels. AEA causes a prolongation of pregnancy in rats and temporarily inhibits the postnatal development of the hypothalamo-pituitary axis in offspring. The action of AEA on the reproductory parameters occurs at both the hypothalamic and pituitary level. CB(1) receptors have also been found in the anterior pituitary. Further, LH levels in CB(1) receptor-inactivated mice were decreased compared with wild-type mice.Taken together, all these observations suggest that the endocannabinoid system is playing an important part in the regulation of the mentioned visceral functions and it provides the bases for further applications of cannabinoid receptor agonists and/or antagonists in visceral diseases regulated by the hypothalamus.     

Possible role of the 34-kilodalton hyaluronic acid-binding protein in visceral Leishmaniasis.

Leishmania donovani, the causative organism of human visceral leishmaniasis, invades host macrophages through its interaction with the cell surface molecules of target cells. The presence of a cell surface protein (Mr 34 kDa) having specific affinity toward hyaluronan (HA), a major extracellular matrix component, has been previously reported in macrophage cell lines. In order to identify the possible role of this HA-binding protein (HABP) in leishmaniasis, initially we demonstrated its overexpression in spleen, liver, macrophages, and serum of hamsters infected with L. donovani. We further observed higher levels of HABP in the macrophage cell line J774.G8 upon infection with L. donovani. Finally, we observed a significant increase in the level of HABP in the serum of patients with kala-azar. In order to understand its functional role in leishmaniasis, we report here a significant inhibition of cellular phosphorylation of HABP in hamster macrophages infected with L. donovani. Interestingly, the 34-kDa HABP was shown to bind with 2 proteins of promastigotes as well as amastigotes of L. donovani (with molecular masses of 55 kDa and 30 kDa respectively), suggesting a possible role for HABP in adhesion during the interaction of promastigotes and macrophages.     

The role of taurine in adaptation of visceral systems under psycho-emotional stress in rats

In the recent years, an identification of regulatory mechanisms underlying the general adaptation syndrome as an organism’s response to drastic emotional stress-evoking environmental changes is gaining in its importance. The ability to control over visceral functions plays a crucial role in stress reactions due to a threat of neurodynamic imbalance in sympathetic-parasympathetic relationships with the heart as their most vulnerable element. Fast stress adaptation promotes restoration not only of the sympathetic-parasympathetic balance, but also of energy metabolism. Taurine is one of the major regulatory molecules that activate metabolic processes. The present work addresses the following issues: (1) the descending influence of the paraventricular nucleus (PVN) on neural reaction of the solitary tract nucleus (STN), which is the first link in the visceral sensitivity pathway, (2) the mechanisms of central control over visceral reactions as investigated by mathematical modelling and analysis of the heart rate variability (HRV), and (3) morphofunctional changes in brain structures, integrating and regulating the visceral sphere (hypothalamic PVN, amygdala), under psycho-emotional stress with and without intraperitoneal injection of taurine (50 mg/kg). Acute and semichronic experiments were conducted on white nonlinear rats under 5-h immobilization stress. An extremely strong centralization of the vegetative HRV parameters (HR, VBI, SSTI) was revealed, with these parameters normalized on days 7 and 14 post taurine injection. An interaction and interdependence of the central regulatory mechanisms of cardiovascular reactions as well as a considerable protective role of taurine, promoting fast restoration of adaptive properties of the central and peripheral visceral sensitivity components under the development of long-term psycho-emotional stress, were shown.     

The role of IL15 gene variants in visceral leishmaniasis among Iranian patients

The role of IL-15 in the protection against Leishmania (L) parasites has been clarified in previous studies, in which IL-15 similar to IFN-γ induces IL-12 production and stimulates the leishmaniacidal activity of the macrophages infected with L. infantum. Furthermore, the increased level of IL-15 in acute visceral leishmaniasis patients (VL) can suppress Th2 cytokines such as IL-4. Since different single nucleotide polymorphisms (SNPs) in the IL15 gene have been described, this study aimed to investigate the association of the SNPs at the positions 267, 367, 13,687 and 14,035 with VL. The IL15 gene variants were compared between two groups consisting of 117 VL patients and 146 healthy individuals using polymerase chain reaction-restriction fragment length polymorphism. The results showed that the frequencies of the alleles 267C (83.9 vs. 73.5 %, P = 0.0035), 13687A (22.4 vs. 12.8 %, P = 0.032), genotype 267CC (68.5 vs. 55.6 %, P = 0.031), haplotypes CGCA (16 vs. 8.3 %, P = 0.02) and TACA (11.2 vs. 4.8 %, P = 0.02) were significantly higher in the controls than those in the patients, while the genotypes 267TT (8.5 vs. 0.7 %, P = 0.0016), 13687CC (78.6 vs. 65.5 %, P = 0.015), the haplotypes TGCT (10 vs. 2.5 %, P = 0.00002) and TGCA (5.7 vs. 0.35 %, P = 0.000001) were significantly more frequent in the patients. In conclusion, it may be speculated that these gene variants with probable effects on the IL-15 production can serve as the factors influencing VL among Iranian population. However, to clarify the association of these variants with the level of IL-15, further studies are recommended.     

雌激素在肠易激综合征内脏高敏感性机制中作用的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以慢性腹部疼痛和排便习惯改变为特征的功能性胃肠病,女性多发,发病率随年龄增加逐渐降低,绝经期雌激素替代治疗又加重了肠易激综合征的发病率,提示这种性别差异与雌激素水平有关。目前内脏高敏感性机制被认为是IBS的特征性病理生理学基础,雌激素影响内脏高敏感性的机制还不清楚。研究表明,雌激素可以通过脊髓-中枢途径和自主神经途径影响内脏感觉,雌激素影响迷走神经功能可能是内脏高敏感性的机制之一。本文综述近年来有关雌激素与内脏高敏感性之关系的研究。     

The role of proctolin and glutamate in the excitation-contraction coupling of insect visceral muscle

Proctolin (1 X 10(-10) to 1 X 10(-9) M) had a minimal effect on the spontaneous and evoked electrical events of the hindgut of the cockroach Leucophea maderae. Spontaneous action potentials and contractile activity stopped when the hindgut was exposed to 2 mM Mn2+. Eighty per cent of the response of the hindgut to glutamate was blocked by manganese, but only 35% of the response to proctolin. Hindguts were responsive to proctolin in a calcium-free medium, but not to glutamate. Moreover, proctolin appeared to facilitate the reentry of calcium after depleted preparations were returned to normal levels of external calcium. The results offer evidence for two calcium transmembrane channels in insect visceral muscle.     

The role of cell interactions in the control of lymphocyte traffic.

The effect of pretreatment of ⁵¹Cr-labelled lymph node cells with neuraminidase, trypsin, phospholipase A, Con A and LPS on their fate in intact and splenectomized recipients following intravenous injections was studied. Decreased lymph node entry was observed in all experimental groups in which intact mice were used as recipients. Evidence for this decrease to be the result of a change in the interaction of the circulating cells with the cells in the liver, lungs or spleen and not the result of a specific defect of the interaction between the lympocytes and the post-capillary venule endothelium is presented and discussed.     

The role of cell interactions in the differentiation of teratocarcinoma-derived parietal and visceral endoderm

Cell interactions have been implicated in the differentiation of visceral and parietal endoderm in the developing mouse embryo. Embryoid bodies formed from F9 embryonal carcinoma cells have been useful in characterizing the events which lead to endoderm formation. As part of our effort to specify the interactions which may be involved in this process we have isolated visceral endoderm-like cells (VE) from F9 embryoid bodies and cultured them under various conditions. Using a combination of immunoprecipitation and enzyme-linked immunosorbent assay, we demonstrate that monolayer culture of these cells on a number of different substrates leads to a dramatic decrease in the level of alphafetoprotein (AFP), a VE-specific marker. Northern blot analysis of AFP mRNA indicates very low levels of this message are present after 48 hr in monolayer culture. Coincident with the drop in AFP levels is an increase in the levels of the cytokeratin Endo C and tissue plasminogen activator, both markers for parietal endoderm (PE). Morphological evidence at the ultrastructural level supports a transition from VE to PE. In contrast, the VE phenotype can be maintained in vitro by interaction with aggregates, but not monolayers, of stem cells. In addition, culturing the cells on the curved surface of gelatin-coated dextran beads, but not on a flat gelatin surface facilitates AFP expression and the cells are morphologically intermediate between VE and PE cells. The potential role of junctional complexes and cell shape are discussed.