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

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

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

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

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

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 < 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

Menopause affects pain depending on pain type and characteristics

OBJECTIVE: Women are more affected than men by many chronic pain conditions, suggesting the effect of sex-related mechanisms in their occurrence. The role of gonadal hormones has been studied but with contrasting results depending on the pain syndrome, reproductive status, and hormone considered. The aim of the present study was to evaluate the pain changes related to the menopausal transition period. METHODS: In this observational study, postmenopausal women were asked to evaluate the presence of pain in their life during the premenopausal and postmenopausal periods and its modification with menopause. RESULTS: One hundred one women were enrolled and completed questionnaires on their sociodemographic status, pain characteristics, and evolution. The most common pain syndromes were headache (38%), osteoarticular pain (31%), and cervical/lumbar pain (21%). Pain was present before menopause in 66 women, ceased with menopause in 17, and started after menopause in 18. Data were used for cluster analysis, which allowed the division of participants into four groups. In the first, all women experienced headaches that disappeared or improved with menopause. The second group included osteoarticular pain; the pain improved in half of these women and remained stable in the other half. The third group had cervical/lumbar pain, which disappeared or improved with menopause in all. The fourth group presented different kinds of moderate pain, which worsened in all. CONCLUSIONS: The present study provides preliminary data suggesting that menopause can affect pain depending on the painful condition experienced by the woman. This underlines the different interactions of menopause-related events with body structures involved in pain

A pain educational program for pediatric nurses: topics and key points

The undertreatment of pain in children may lead to severe consequences. Basic knowledge about pain in this category of patients may improve pain assessment and its management. In line with the Project established by the Italian Ministry of Health, authors planned an educational program devoted to the pediatric nurses. The concept of brain and of cognitive development, the methodological bases of the pain measurement and the cognition of long-term consequences on pain have been the key points of the program. The course was efficacious and highly appreciated by nurses. The improvement of practice standards will be the true indicator of its efficacy

Cefalea e dolore muscoloscheletrico in adolescenti in età scolare

La cefalea, così come il dolore muscolo-scheletrico, è tra i dolori più diffusi nei bambini e negli adolescenti. Al fi ne di conoscere la prevalenza di questi dolori e l’eventuale associazione con alcune abitudini di vita nella nostra società, è stato condotto uno studio su 110 bambini di una scuola media della Toscana. Ventisei studenti hanno riferito cefalea o dolore muscolo-scheletrico e sessantanove hanno lamentato entrambi. La cefalea era preminente nelle femmine (53% vs 46%), mentre il dolore muscolo-scheletrico era maggiormente rappresentato nei maschi (54% vs 46%). Il mal di schiena era presente soprattutto al risveglio (24%) o in seguito a posizione seduta (11,5%), mentre il trasporto dei libri scolastici si accompagnava spesso a dolore muscolare (47%). L’ attività sportiva era associata a dolori muscolo-scheletrici (72%), così come l’ipermotilità forzata e prolungata (63%). Da questo studio emerge che la presenza di dolore è particolarmente elevata nei soggetti in età scolare e che alcune abitudini di vita sono associate alla sua comparsa