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Giovanni Cucchiaro

Publications and source records attributed to Giovanni Cucchiaro.

8 recordsLinked to original sources

The locus coeruleus nucleus as a site of action of the antinociceptive and behavioral effects of the nicotinic receptor agonist, epibatidine.

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the locus coeruleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the locus coeruleus (LC), and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either ACSF, epibatidine (0.01, 0.06, 0.12, and 0.3mug) into the locus coeruleus or epibatidine (2.5-5mug/kg) subcutaneously. Assessment of pain-related behavior was done by evaluating the incidence of favoring, lifting and licking of the injected paw in the different groups. Abnormal motor behavior was also recorded. Infusion of epibatidine into LC induced analgesia, which was reversed by prior infusion of mecamylamine into LC. Epibatidine into the locus coeruleus resulted in a significant lower pain score in the second phase of the formalin test compared to control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that the administration of epibatidine outside the locus coeruleus area was not analgesic. The every tested dose of epibatidine administered into the locus coeruleus also produced freezing behavior immediately after injection, which was relatively short-lived compared to the analgesic effect. Freezing was inhibited by administration of mecamylamine into the LC. Together the results implicate the LC as a target for the analgesic effects of epibatidine.

Analgesics↗

What postoperative outcomes matter to pediatric patients?

Children are often excluded from making decisions related to their medical treatment, and parents' proxy reports are often used. This approach fails to consider that parents and children may differ in their perception of the child's health. In this study, we assessed children's decision-making processes related to postoperative pain management. Forty-five children who underwent an anterior cruciate ligament repair or Nuss procedure for pectus excavatum repair were studied. A standard gamble technique was used to assess children's perceptions of the utility of a hypothetical treatment that would provide them with perfect pain control, with respect to different rates of risk for vomiting during the postoperative period. The maximum risk of vomiting that the overall study population was willing to accept to decrease the pain level to zero was 32% +/- 24%. Girls were willing to take a significantly higher risk (41% +/- 24%) compared to boys (25% +/- 22%) (P = 0.02). Children who actually experienced vomiting before they were questioned were willing to take a higher risk (46% +/- 26%) compared to those who did not (23% +/- 17%) (P = 0.035). Children can express opinions about preferred postoperative outcomes and provide useful input about their care. Girls, more than boys, seem to perceive vomiting as less important than improved pain control in the postoperative period.

Adolescent↗

A comparison of epidural bupivacaine-fentanyl and bupivacaine-clonidine in children undergoing the Nuss procedure.

The administration of epidural opioids, though effective for producing analgesia, has severe side effects in most patients. It is unknown whether clonidine can effectively replace opioids and cause fewer side effects. We compared, in this randomized trial, the incidence of vomiting and pruritus as well as the analgesic profile of three different combinations of bupivacaine, fentanyl, and clonidine administered epidurally in patients undergoing the Nuss procedure: bupivacaine + fentanyl, bupivacaine + clonidine, bupivacaine + fentanyl + clonidine. The incidence of side effects was significantly less in the bupivacaine + clonidine group (33%) compared with the bupivacaine + fentanyl (92%) and bupivacaine + fentanyl + clonidine (73%) groups (P = 0.004). Quality of postoperative analgesia was similar in the three groups. No significant complications were observed. In conclusion, clonidine is an effective and safe alternative to epidural opioids.

Adolescent↗

Intraarticular bupivacaine-clonidine-morphine versus femoral-sciatic nerve block in pediatric patients undergoing anterior cruciate ligament reconstruction.

We hypothesized that combined femoral-sciatic nerve block (FSNB) offers better analgesia with fewer side effects than intraarticular infiltration (IA) in children undergoing anterior cruciate ligament (ACL) reconstruction. Thirty-six children undergoing ACL reconstruction were randomized to FSNB or IA. FSNB patients had FSNB with bupivacaine (0.125%)-clonidine (2 microg/kg), whereas IA patients received bupivacaine (0.25%)-clonidine (1 microg/kg)-morphine (5 mg). Postoperatively, analgesia was provided with patient-controlled analgesia and rescue morphine. Patient demographics were similar. FSNB patients required less intraoperative fentanyl (50 +/- 40 microg versus 80 +/- 50 microg; P = 0.04). Visual analog scale score for FSNB was smaller than IA in the recovery room (1.8 +/- 3 versus 5.4 +/- 3; P = 0.0002) and during the first 24 h (1.6 +/- 1 versus 2.9 +/- 2; P = 0.01)). FSNB morphine use in the first 18 h was less (7 +/- 13 mg versus 21 +/- 21 mg; P = 0.03). Fewer FSNB patients vomited (11% versus 50%; P = 0.03). IA patients required morphine patient-controlled analgesia sooner. After ACL reconstruction in children, FSNB with bupivacaine-clonidine provides better analgesia with fewer side effects than IA with bupivacaine-clonidine-morphine.

Adolescent↗

The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the alpha4 nicotinic receptor agonist epibatidine.

The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the dorsal raphe and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either epibatidine (0.01, 0.015, 0.03, and 0.06 microg) in the dorsal raphe or epibatidine (2.5-5 microg/kg) subcutaneously. Assessment of pain related behavior was done evaluating the incidence of favoring, lifting, and licking of the injected paw in the different groups. Abnormal behavior (freezing) was also recorded. Epibatidine was at least 100 times more potent when administered into the dorsal raphe nucleus versus systemically, implicating this nucleus as a site of action of the analgesic effects of epibatidine. Thus, epibatidine (0.015, 0.03, and 0.06 microg) in the dorsal raphe resulted in a significant lower pain score in the second phase of the formalin test compared with control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that administration of epibatidine within the periaqueductal gray area but outside the dorsal raphe area was not analgesic. The highest doses of intraraphe epibatidine (i.e., 0.03-0.06 microg) also produced "freezing" behavior immediately after injection, which was relatively short-lived compared with the analgesic effect. Together, the results implicate the dorsal raphe nucleus as a target for the analgesic and perhaps anxiogenic effects of epibatidine.

Analgesics↗

Blood glucose control during selective arterial stimulation and venous sampling for localization of focal hyperinsulinism lesions in anesthetized children.

Surgical management of congenital hyperinsulinism is improved by accurate localization of small, focal dysregulated pancreatic lesions using the arterial stimulation and venous sampling (ASVS) test, which can demonstrate increased hepatic venous insulin concentrations after selective arterial injections of calcium. However, anesthesia-related increases in blood glucose can induce insulin secretion, making it difficult to interpret ASVS test data. In this retrospective study, we examined the effect of anesthetic interventions on blood glucose concentrations in 68 children undergoing ASVS testing. We considered only the glucose concentrations observed before calcium stimulation in the final analysis. The choice of drugs for induction (sevoflurane, propofol, or thiopentone), maintenance inhaled anesthetics (sevoflurane, desflurane, or isoflurane), and the use of caudal epidural bupivacaine were not associated with significant differences in the mean blood glucose concentration before ASVS. However, patients receiving remifentanil infusions had smaller mean glucose concentrations (80 +/- 18 versus 100 +/- 44 mg x dl(-1), P = 0.01). These concentrations were also significantly smaller if tracheal intubation was delayed for at least 10 min after induction while patients received inhaled anesthetics via a face mask along with remifentanil infusions (79 +/- 14 for delayed intubation versus 95 +/- 39 mg x dl(-1) for early intubation, respectively, P = 0.03). The percentage increase in glucose concentrations from preintubation values was significantly smaller in these subjects (3.7% +/- 21.9% for delayed intubation versus 31.7% +/- 60.4% for early intubation, P = 0.02). We conclude that the anesthetic management protocol for these patients should include the use of remifentanil infusions and the administration of inhaled anesthetics and remifentanil infusions for a minimum of 10 min to establish a deep plane of anesthesia before tracheal intubation.

Adolescent↗

Alpha 4 nicotinic acetylcholine receptor subunit links cholinergic to brainstem monoaminergic neurotransmission.

Agonists of nicotinic receptors containing the alpha4-subunit produce antinociception accompanied by several adverse side effects. The purpose of this study was to determine the distribution of the alpha4-subunit of nicotinic acetylcholine receptors (nAChR) in brainstem monoaminergic nuclei that may contribute to these effects using dual labeling immunofluorescence methods. The alpha4-subunit immunoreactivity was enriched in serotonergic (nucleus raphe magnus, pallidus, obscurus, and dorsalis) and noradrenergic (A5, locus coeruleus (LC), A7) areas associated with antinociception, where it was commonly colocalized with serotonin (5-HT) or tyrosine hydroxylase (TH) immunoreactivity. However, it was also noted that alpha4 was present in all other brainstem monoaminergic nuclei examined (adrenergic C1-C3, noradrenergic A1-alpha4, dopamine A9 and A10, nucleus raphe medianus). To determine if alpha4 agonists could impact neural activity in brainstem, monoaminergic nuclei that are associated with antinociception, the expression of c-Fos in response to the systemic administration of epibatidine (2.5, 5, or 10 microg/kg) was examined. Epibatidine produced a robust (2-5-fold) increase in c-Fos expression, which was not dose dependent, in all of these areas examined except the nucleus raphe magnus. These results suggest that the alpha4 subunit is positioned to mediate the effects of acetylcholine widely across many, if not all, monoaminergic neurons in the brainstem. These observations emphasize the potential involvement of noradrenergic, as well as serotonergic mechanisms in epibatidine's analgesic effects, and they also suggest that even selective alpha4 ligand may have widespread effects on brain monoamine neurotransmission.

Animals↗