Cardiocirculatory intraoperative assessment during single-shot caudal anaesthesia in children: comparison between levobupivacaine and ropivacaine

BACKGROUND: Caudal block with levobupivacaine or ropivacaine is the most commonly used regional anaesthesia in children. METHODS: The aim of study was to compare the cardiocirculatory profile induced in two matched groups of young patients, submitted to caudal anaesthesia with levobupivacaine or ropivacaine for an elective subumbilical surgery. Sixty children were enrolled: thirty received levopubivacaine 0.25% and thirty ropivacaine 0.2%. Intraoperative heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) were monitored at following times: Ta0 (after anaesthesia induction), Tal (after caudal anaesthesia), Ta2 (five minutes later), Ta3 (ten minutes later), Ts1 (at surgical incision), Ts2, Ts3, Ts4, Ts5 (every 10 minutes during surgery), Taw (at the awakening). RESULTS: In both groups the cardiocirculatory trend remained within normal ranges at all times considered, demonstrating the safety of the method with both drugs. Both groups showed a similar trend at the different monitoring times: low decrease in HR, SBP and DBP after caudal block, slight increase in parameters after skin incision, slight decrease during surgery, increase at awakening. Regarding SBP and DBP, the levobupivacaine group children generally showed higher levels compared to the ropivacaine group, especially for DBP. CONCLUSIONS: Paediatric caudal anaesthesia is an effective method with an very infrequent complication rate. Possible hypotheses for differing haemodynamic behaviour could include a stronger vasoconstriction reflex of innervated areas during caudal anaesthesia with levobupivacaine and a lower levobupivacaine induced block of the sympathetic fibers, related to different pharmacokinetic profile of low concentrations of the local anaesthetics used in paediatric epidural space

Quantitative Real-Time PCR detection of TRPV1–4 gene expression in human leukocytes from healthy and hyposensitive subjects

<p>Abstract</p> <p>Background</p> <p>Besides functioning as chemosensors for a broad range of endogenous and synthetic ligands, transient receptor potential vanilloid (TRPV) 1–4 channels have also been related to capsaicin (TRPV1), pain, and thermal stimuli perception, and itching sensation (TRPV1–4). While the expression of the TRPV1–4 genes has been adequately proved in skin, sensory fibres and keratinocytes, less is known about TRPV3 and TRPV4 expression in human blood cells.</p> <p>Results</p> <p>To study the gene expression of TRPV1–4 genes in human leukocytes, a quantitative Real-Time PCR (qRT-PCR) method, based on the calculation of their relative expression, has been developed and validated. The four commonly used house-keeping genes (HKGs), β-Actin (Act-B), glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxanthine ribosyltransferase (HPRT1), and cyclophilin B (hCyPB), were tested for the stability of their expression in several human leukocyte samples, and used in the normalization procedure to determine the mRNA levels of the TRPV 1–4 genes in 30 healthy subjects. cDNAs belonging to all the TRPV1–4 genes were detected in leukocytes but the genes appear to be expressed at different levels. Our analysis did not show significant sex differences in TRPV1–4 cDNA levels in the 30 healthy subjects. The same qRT-PCR assay was used to compare TRPV1–4 expression between healthy controls and patients hyposensitive to capsaicin, pain and thermal stimuli: an almost doubled up-regulation of the TRPV1 gene was found in the pathological subjects.</p> <p>Conclusion</p> <p>The qRT-PCR assay developed and tested in this study allowed us to determine the relative expression of TRPV1–4 genes in human leukocytes: TRPV3 is the least expressed gene of this pool, followed by TRPV4, TRPV1 and TRPV2. The comparison of TRPV1–4 gene expression between two groups of healthy and hyposensitive subjects highlighted the evident up-regulation of TRPV1, which was almost doubly expressed (1.9× normalized fold induction) in the latter group. All the four house-keeping genes tested in this work (Act-B, GAPDH, hCyPB, HPRT1) were classified as optimal controls and showed a constant expression in human leukocytes samples. We recommend the use of these genes in similar qRT-PCR studies on human blood cells.</p

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-Type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs. awx326media1 5680039660001 The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.We thank the Medical Research Council (J.J.C., Career Development Award, G1100340), Wellcome Trust (200183/ Z/15/Z and 101054/Z/13/Z) and Arthritis Research UK (20200) for generous support and Shionogi for an academic research grant (165302). Thanks to the University of Siena for partially funding this research. J.T.B. is supported by a Research Fellowship from the Alzheimer�s Society. J.D.R. received funding from the Wellcome Trust through the London Pain Consortium and from Colciencias through a Francisco Jose de Caldas Scholarship (LASPAU, Harvard University). D.L.H.B. is a Wellcome senior clinical scientist (ref. no. 095698z/11/z and 202747/Z/16/Z) and member of the Wellcome Pain Consortium.Scopu

Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

Background: Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent painrelated behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings: In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance: These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight th

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A uniquepowerful approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. BAC transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human paininsensitive phenotype are therefore potential novel targets for the development of new analgesic drugs

Severe withdrawal syndrome in three newborns subjected to continuous opioid infusion and seizure activity dependent on brain hypoxia--ischemia. A possible link.

BACKGROUND: The aim of this investigation was to verify whether brain hypoxia represented a risk factor for the occurrence and severity of opioid abstinence syndrome. METHODS: Three newborns who manifested seizure activity as a result of hypoxia, focal brain ischemia, and hypoxia and sepsis, respectively, were compared with 17 neonates who suffered from hypoxia without developing seizure activity. RESULTS: The first three neonates suffered a severe withdrawal syndrome (a rating on the neonatal abstinence score>17), the others did not. CONCLUSIONS: It is hypothesized that brain hypoxia facilitated the occurrence and severity of the withdrawal syndrome because some key neurochemical processes (such as N-methyl-D-aspartate activation, protein kinase C activation and nitric oxide production) are common to both phenomena

Sensory phenotype assessment in a young girl affected by congenital insensitivity to pain (CIPA)

Sensory phenotype was assessed in a young girl affected by congenital insensitivity to pain (CIPA) scheduled for an open surgical drainage. The sensory profile showed that only the Abeta fibers were functioning normally, whereas Adelta and C fibers did not respond to nociceptive stimuli. On the basis of these findings and the results of cardiovascular reflexes, she was submitted to abscess incision and debridement under midazolam sedation alone. She did not report pain or other discomfort during surgery. The sensory (and sympathetic) assessment may have a high potential value in planning anesthesia and analgesia in children with CIPA. This psychophysical procedure could be introduced as standard component of clinical evaluation before surgery

Increase of plasmatic beta-endorphin immunoreactive material in children in the perioperative period: the influence of the site of surgery

BACKGROUND: The primary aim of the study was to confirm the increase of plasmatic IR beta-endorphin material during the perioperative period in children. The second was to search for the factors responsible for this increment. METHODS: Seventy-two consecutive children undergoing a surgical procedure were recruited. Pre-anaesthesia and anaesthesia were standardised. Plasmatic IR beta-endorphin material was measured at three timepoints: at baseline (t (0)), before induction (t (1)), and at the end of anaesthesia (t (2)). Two general linear models were set up to analyse the influence of demographics and clinics on the IR beta-endorphin variation between t (0) and t (1). A third model was established to process the possible surgical factors contributing to the IR beta-endorphin variation between t (1) and t (2). RESULTS: ANOVA showed that IR beta-endorphin concentrations increased significantly across the three timepoints (p &lt; 0.0001). Wilcoxon test proved that the difference was significant both for t (0) vs. t (1) and for t (1) vs. t (2). None of the factors taken into account in the pre-operative period influenced the increase in IR beta-endorphin between t (0) and t (1). Of the factors taken into account in the surgical period, only the type of procedure was significant (p = 0.005). The t-test showed that IR beta-endorphin significantly increased during spermatic and epigastric anastomosis (p = 0.000), orchidopexy (p = 0.02), Van der Meulen urethroplasty (p = 0.004), and Duckett urethroplasty (p = 0.003). CONCLUSION: Plasmatic beta-endorphin increases during the perioperative period in children. The site of surgery is responsible for this increment during intervention