Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I.

The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats.

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.

Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats.

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain.

The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.

Pathogenesis and Surgical Treatment of Congenitally Corrected Transposition of the Great Arteries (ccTGA): Part III.

Congenitally corrected transposition of the great arteries (ccTGA) is an infrequent and complex congenital malformation, which accounts for approximately 0.5% of all congenital heart defects. This defect is characterized by both atrioventricular and ventriculoarterial discordance, with the right atrium connected to the morphological left ventricle (LV), ejecting blood into the pulmonary artery, while the left atrium is connected to the morphological right ventricle (RV), ejecting blood into the aorta. Due to this double discordance, the blood flow is physiologically normal. Most patients have coexisting cardiac abnormalities that require further treatment. Untreated natural course is often associated with progressive failure of the systemic right ventricle (RV), tricuspid valve (TV) regurgitation, arrhythmia, and sudden cardiac death, which occurs in approximately 50% of patients below the age of 40. Some patients do not require surgical intervention, but most undergo physiological repair leaving the right ventricle in the systemic position, anatomical surgery which restores the left ventricle as the systemic ventricle, or univentricular palliation. Various types of anatomic repair have been proposed for the correction of double discordance. They combine an atrial switch (Senning or Mustard procedure) with either an arterial switch operation (ASO) as a double-switch operation or, in the cases of relevant left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD), intra-ventricular rerouting by a Rastelli procedure. More recently implemented procedures, variations of aortic root translocations such as the Nikaidoh or the half-turned truncal switch/en bloc rotation, improve left ventricular outflow tract (LVOT) geometry and supposedly prevent the recurrence of LVOTO. Anatomic repair for congenitally corrected ccTGA has been shown to enable patients to survive into adulthood.

Pathogenesis and Surgical Treatment of Dextro-Transposition of the Great Arteries (D-TGA): Part II.

Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5-7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood.

Virtual simulations in planning intravascular treatment of aortic coarctation - a retrospective analysis.

Introduction: A number of studies on using both three-dimensional printing and virtual models in assessment of aortic coarctation have been published, yet none of them uses virtual modelling as a planning tool in a blind retrospective analysis. Aim: Assessment of virtual modelling and virtual reality in planning interventional treatment of aortic coarctation. Material and methods: The study involved computed tomography scans of 20 patients performed prior to interventional treatment of aortic coarctation, which were used to create a virtual three-dimensional model of the aorta in Materialise Mimics. A group of potential stents was modelled in Materialise 3-Matic and complete simulations were assessed in Mimics Viewer using a virtual reality headset in order to choose an optimal stent, which was later compared with the implanted one. Results: In 5 cases identical or very similar stents were proposed, in 12 cases simulations had slight, potentially avoidable misestimations either in stent length or diameter, and in 3 cases differences were more considerable. Overall, in 14 cases the location of the stent was concordant between the simulation and reality and in the remaining 6 cases the simulated stent was located lower than the actual one. Conclusions: The method of computer modelling provided a satisfactory success rate of predicting the possible stents to use during the procedure. Differences in chosen stents may have been caused by individual experience in interventional cardiology, the lack of availability of certain stents in the heart catheterization laboratory, the lack of information about the diameter of the vascular access and differences in dimensions measured on the model, tomography and angiography.

Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis.

Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns of numerous genes known to be involved in the aberrant modulation of cell cycle steroidogenesis, abnormal hormonal, immune and inflammatory status in endometriosis, apoptosis, adhesion, angiogenesis, proliferation, immune and inflammatory processes, response to hypoxia, steroidogenic pathway and hormone signaling are involved in the pathogenesis of endometriosis. Accumulating evidence suggest that various epigenetic aberrations may contribute to the pathogenesis of endometriosis. Among them, DNA methyltransferases, histone deacetylators, and non-coding microRNAs demonstrate differential expression within endometriotic lesions and in the endometrium of patients with endometriosis. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may contribute to the discovery of a useful prognostic biomarker, which could aid in the future earlier detection, timely diagnosis, and initiation of a new approach to the treatment of endometriosis, as well as inform us about the effectiveness of treatment and the stage of the disease. As the etiology of endometriosis is highly complex and still far from being fully elucidated, the presented review focuses on different approaches to identify the genetic and epigenetic links of endometriosis and its pathogenesis.

Analysis of Let-7 Family miRNA in Plasma as Potential Predictive Biomarkers of Diagnosis for Papillary Thyroid Cancer.

The most common histological type of thyroid cancer is papillary thyroid carcinoma (PTC). Radical resection of the thyroid gland is currently the recommended method of treatment. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies. In this work, using the droplet digital PCR (ddPCR) method, we have analyzed the level of five miRNAs (let-7a, let-7c, let-7d, let-7f, and let-7i) in the plasma of patients with PTC and compared them with those of a healthy control group to investigate whether miRNAs also have value in the management of PTC. Levels of four miRNAs, namely let-7a, let-7c, let-7d, and let-7f, were significantly higher in PTC patients than healthy controls. Thus, the analysis of circulating let-7 can be a useful tool and support the currently used methods for PTC diagnosis. However, our observation requires further research on a larger patient group.

Altered levels of circulating nuclear and mitochondrial DNA in patients with Papillary Thyroid Cancer.

Papillary thyroid cancer is the most common thyroid cancer type. However, diagnostics based on fine needle biopsy cannot make a definitive diagnosis in 25% of thyroid nodules. Additionally, approximately 70% to 80% of thyroid lobectomies performed just for diagnostic purposes are benign. Despite this, biopsy still remains the main method of evaluation of thyroid nodules. Cell-free DNA (cf-DNA) measurement could give a new diagnostic opportunities which may reduce the number of unnecessary thyroid procedures. In this study, using a qPCR, we have examined the nuclear cf-DNA and mitochondrial cf-DNA in the plasma of 32 patients. We have found that the level of nuclear cf-DNA is almost 2-fold increased (median 3 089 vs. 1 872, p = 0.022), whereas mitochondrial cf-DNA content was significantly decreased in respect to healthy controls (median 44 992 vs. 92 220, p = 0.010). The ROC curve analysis showed high specificity for nuclear cf-DNA and mitochondrial cf-DNA, which may serve as a useful tool to decrease the number of unneeded surgeries. Our study reports the first epidemiological evidence for lower mitochondrial cf-DNA content in the patient group, what suggests that apart from nuclear cf-DNA also mitochondrial cf-DNA is affected by disease development.

Potential of Liquid Biopsy in Papillary Thyroid Carcinoma in Context of miRNA, BRAF and p53 Mutation.

BACKGROUND: Liquid biopsy is a minimally invasive detection method for molecular biomarkers such as miRNA and cell free DNA in body fluids. Deregulations of miRNA are involved in papillary thyroid carcinoma (PTC), one the most common endocrine malignancy. The most widespread common mutations detected in papillary thyroid cancers are BRAF mutations. Many studies indicate that the BRAF mutation is related to deregulation of miRNA. p53 has an important role in cell cycle control, DNA repair and apoptosis. Moreover, the p53 can regulate the expression of miRNAs and thus participate in thyroid oncogenesis. OBJECTIVE: In this review, we briefly summarize the present state of knowledge about miRNA, BRAF and p53 mutation in the development of PTC and the possibility of using detecting BRAF mutation and miRNA expression in liquid biopsy. RESULTS: The use of the plasma miRNA expression profile in combination with the BRAF mutation analysis in cf-DNA may be a valuable tool in management of PTC. CONCLUSION: Numerous molecular variation characterize recent diagnostic and prognostic markers and therapeutic targets for this type of cancer, which offer unique chances for further research and clinical development of innovative treatment strategies for thyroid cancer.

Assessment and pathophysiology of pain in cardiac surgery.

Analysis of the problem of surgical pain is important in view of the fact that the success of surgical treatment depends largely on proper pain management during the first few days after a cardiosurgical procedure. Postoperative pain is due to intraoperative damage to tissue. It is acute pain of high intensity proportional to the type of procedure. The pain is most intense during the first 24 hours following the surgery and decreases on subsequent days. Its intensity is higher in younger subjects than elderly and obese patients, and preoperative anxiety is also a factor that increases postoperative pain. Ineffective postoperative analgesic therapy may cause several complications that are dangerous to a patient. Inappropriate postoperative pain management may result in chronic pain, immunosuppression, infections, and less effective wound healing. Understanding and better knowledge of physiological disorders and adverse effects resulting from surgical trauma, anesthesia, and extracorporeal circulation, as well as the development of standards for intensive postoperative care units are critical to the improvement of early treatment outcomes and patient comfort.

[Atrioventricular nodal and atrioventricular reentrant tachycardia in a patient with Ebsteinanomaly--the role of percutaneous RF ablation, surgery and Amplatzer septal occluder]. / Dwie postacie czestoskurczu nawrotnego u chorej z zespolem Ebsteina przyczyna ekwiwalentów zespolu MAS.Rola przezskórnej ablacji, operacji i zapinki Amplatza.

We present a case of a twelve-year-old girl with Ebstein's anomaly, atrial septal defect and two forms of tachycardia. From the first year the patient suffered from episodes of tachycardia. A few months prior to admission, episodes of palpitations became more frequent, periodically incessant and difficult to interrupt, despite amiodarone treatment. During the tachycardia the patient deteriorated with severe cyanosis, hypotension and often with syncope. During sinus rhythm ECG showed RA enlargement and preexcitation. During the documented tachycardia with rate 160-170/min, the ECG showed right bundle branch block (QRS=160 ms) with right axis deviation. An echocardiogram demonstrated dislodgment of septal tricuspid leaflet 30 mm with a high degree of right ventricle atrialisation, moderate tricuspid insufficiency, and ASD with bidirectional shunt. During the EP study two forms of tachycardia were induced: orthodromic atrioventricular reentrant tachycardia, and atrioventricular nodal reentry tachycardia. Both tachycardias were successfully ablated. Four months later the patient underwent TV replacement with aortic homograft, Glenn anastomosis and ASD closure with fenestration. During the next 18 months, the patient was in better general condition, but still was cyanotic especially during exercise (SAT 76%). An Amplatzer occluder was implanted on the 'residual' atrial septal defect. During the 24-month follow-up period, the patients has been in a good general condition, showing good exercise tolerance with no cyanosis or arrhythmia.

Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats.

BACKGROUND AND PURPOSE: Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles. EXPERIMENTAL APPROACH: The study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures. KEY RESULTS: Perfusion of cerebral ventricles with anandamide (AEA), endomorphin-2 (EM-2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM-2, URB597 and JZL195 was blocked by CB1 receptor antagonist, AM251 and by µ receptor-antagonist, ß-funaltrexamine. In contrast to AEA, 2-arachidonoylglycerol alone did not decrease ETJ amplitude. CONCLUSIONS AND IMPLICATIONS: We demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM-2-induced antinociception was mediated by µ and CB1 receptors. The action of AEA and EM-2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.

Opioid and Cannabinoid System in Food Intake.

Energy intake and expenditure are regulated by a complex network of neurochemical systems. The results of numerous studies have provided information about receptors involved, the sites of action within the brain and interactions between various systems, including opioid and cannabinoid, in regulation of energy balance. This review summarizes our present knowledge on the opioid and cannabinoid system appetite and satiety pathways. The involvement of the three main types of opioid receptors (MOR, DOR and KOR) and CB1 cannabinoid receptor, as well as the endogenous ligands of these receptors in food intake is documented. Finally, the use of opioid-cannabinoid system interactions as a new approach in the search for the next generation therapeutics controlling food intake disorders is discussed.

Prognosis in children with pulmonary arterial hypertension: 10-year single-centre experience.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary arterioles with an unfavourable prognosis. AIM: To evaluate survival and prognostic factors in patients with PAH diagnosed and treated at a single centre in the years 2004­2013. METHODS: The study included 55 children (33 girls; 66%, 22 boys; 33%), with an average age 6.2 ± 6.0 years, with idiopathic PAH ­ n = 23 (42%), PAH associated with systemic-to-pulmonary shunts ­ n = 17 (31%), and PAH after corrective cardiac surgery ­ n = 15 (27%). Forty-seven of them (87%) were treated with advanced therapy. RESULTS: During the follow-up with an average time of 5.6 ± 4.7 years 15 (27.3%) children died. The one-, three-, five-, and ten-year survival was, respectively, 83.1%, 77.1%, 70.7%, and 65.2%. The analysis of the survival curves revealed a better prognosis in patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level < 605 pg/mL (p = 0.024) and a higher probability of survival of three and five years in children at baseline I/II World Health Organisation functional class (WHO-FC). The higher risk of death was associated with a higher pressure in the right atrium (HR 1.23, p < 0.01) and higher pulmonary resistance (HR 1.1, p < 0.01), whereas no history of syncope had a better prognosis (HR 0.31, p = 0.03). CONCLUSIONS: Survival in the study group was comparable to the currently published register data. Mortality risk factors were connected with the severity of the disease at diagnosis.

Effects of centrally administered vasopressin on orofacial pain perception in rats.

Vasopressin (AVP) appears in the cerebrospinal fluid and plays an important role in nociceptive modulation in the central nervous system. The effect of increased concentration of AVP in the cerebrospinal fluid on the excitability of the hypoglossal nerve nucleus was investigated. The experiments were carried out on rats under chloralose anesthesia. Amplitudes of the retractory evoked tongue jerks (ETJ) of the outstretched tongue during the perfusion of cerebral ventricles with solutions containing AVP or its antagonists and also opioid and serotonin antagonists were recorded. Perfusion of the ventricles with AVP in 100 microM concentration suppressed the ETJ amplitude to 66 +/- 3.83%, and in 200 microM concentration, to 53 +/- 3.18% of the control. V1 vasopressin receptor antagonist, d(CH2)5,Tyr(Me)AVP, blocked the suppressive effect caused by cerebral ventricle perfusion with AVP from 64 +/- 4.11% to 83 +/- 1.58%, whereas V2 vasopressin receptor antagonist, d(CH2)5[Ile2, Ile4]AVP, did not block the antinociceptive effect of AVP. Analgesic effect of AVP was also inhibited by opioid and serotonin receptor antagonists, naloxone and methysergide, respectively. Naloxone blocked the suppressive effect of 100 microM AVP from 64 +/- 5.63% to 92 +/- 3.70% and methysergide from 65 +/- 3.62% to 80 +/- 2.72% of the control. The results indicate that exogenous AVP plays an antinociceptive role in the brain of rats penetrating the lining of the cerebral ventricles into the cerebrospinal fluid and exerting a modulating effect on the tongue motor center situated near III and IV cerebral ventricle. V1 vasopressin receptor, but not V2 vasopressin receptor, is involved in this activity in the CNS. The antinociception of AVP seems to be mediated by opioid and serotonergic pathways.

Inhibition of trigemino-hypoglossal reflex in rats by oxytocin is mediated by mu and kappa opioid receptors.

Recent studies showed that oxytocin plays an important role in the modulation of pain at different levels of the central nervous system. The present study was undertaken to investigate the effect of oxytocin on trigemino-hypoglossal reflex in rats. With the experimental settings used in this study, we have demonstrated that oxytocin showed significant analgesic effect after intracerebroventricular administration in rats, as assayed by the amplitude of the retractory movements of the tongue after tooth pulp stimulation. Antinociceptive effect of oxytocin was inhibited by subsequent perfusion of cerebral ventricles with oxytocin antagonist, [deamino-Cys1-D-Tyr(OEt)2-Thr4-Orn8]-oxytocin, atosiban. An involvement of opioid system in the oxytocin-induced analgesia was studied after intracerebroventricular administration of different opioid antagonists: non-selective naloxone, mu-selective beta-funaltrexamine, delta-selective naltrindole, and kappa-selective nor-binaltorphimine. It was shown that inhibition of antinociceptive effects was mediated through mu and kappa opioid receptors, indicating that there is a synergy between oxytocin and opioid systems in transmitting and modulating pain stimuli. Co-administration of oxytocin and a mu-selective endogenous opioid ligand endomorphin-2 did not significantly increase the antinociceptive activity of endomorphin-2.

Trigemino-hypoglossal somatic reflex in the pharmacological studies of nociception in orofacial area.

Disorders involving the orofacial area represent a major medical and social problem. They are a consequence of central nociceptive processes associated with stimulation of the trigeminal nerve nucleus. A rat model of trigeminal pain, utilizing tongue jerks evoked by electrical tooth pulp stimulation during perfusion of the cerebral ventricles with various neuropeptide solutions, can be used in the pharmacological studies of nociception in orofacial area. The investigated neuropeptides diffuse through the cerebroventricular lining producing an analgesic effect either directly, through the trigemino-hypoglossal reflex arc neurons or indirectly through the periaqueductal central gray, raphe nuclei or locus coeruleus neurons. The aim of this review is to present the effect of pharmacological activity of various neuropeptides affecting the transmission of the sensory information from the orofacial area on the example of trigemino-hypoglossal reflex in rats.

Substance P content in the cerebrospinal fluid and fluid perfusing cerebral ventricles during elicitation and inhibition of trigemino-hypoglossal reflex in rats.

The aim of this study was to establish whether tooth pulp and periaqueductal central gray (PAG) stimulation affects the release of substance P (SP) into the fluid perfusing the cerebral ventricles in rats. The content of substance P in the cerebrospinal fluid and fluid perfusing cerebral ventricles was determined during incisor pulp stimulation with electrical impulses inducing nociceptive trigemino-hypoglossal reflex and then during inhibition of the reflex by stimulation of PAG. Perfusion of the cerebral ventricles was carried out using artificial cerebrospinal fluid (aCSF). SP-like immunoreactivity (SP-LI) was determined in the samples by radioimmunoassay. Samples were collected in four groups: first group-cerebrospinal fluid (CSF); second group-aCSF perfusates without stimulation; third group-aCSF perfusates during incisor pulp stimulation; fourth group-aCSF perfusates during incisor pulp stimulation and simultaneous inhibition of trigemino-hypoglossal reflex by PAG stimulation. It was shown that incisor pulp stimulation led to the increased release of SP-LI into the fluid perfusing cerebral ventricles. Stimulation of PAG reduced the release of SP-LI into the cerebro-ventricular system to the values obtained before the tooth pulp stimulation. The results indicate that PAG significantly inhibits the release of SP-LI into the rat cerebral ventricular system and may be involved in the inhibition of trigemino-hypoglossal reflex.