Nanoanesthesia: a novel, intravenous approach to ankle block in the rat by magnet-directed concentration of ropivacaine-associated nanoparticles.

BACKGROUND: As an alternative to current methods of local nerve block, we studied the feasibility of producing ankle block in the rat with IV injection of magnetic nanoparticles (MNPs) associated with ropivacaine and application of a magnet at the ankle. METHODS: The anesthetic effect of magnet-directed ropivacaine-associated MNPs (MNP/Ropiv) was tested in the rat using paw withdrawal latencies from thermal stimuli applied to the hindpaw. The MNP/Ropiv complexes consisted of 0.7% w/v ropivacaine and 0.8% w/v MNPs containing 12% w/w magnetite (F3O4). The effect of IV injection of MNP/Ropiv with 15, 30, and 60-minute magnet application to the right ankle was compared with the effect without magnet application on the left hindpaw, to conventional ankle block with 0.1% or 0.2% ropivacaine, and to IV injection of MNPs alone with 30-minute magnet application to the right ankle. In addition, the pharmacokinetics of the MNP/Ropiv complexes were determined. RESULTS: IV injection of MNP/Ropiv with magnet application at the ankle significantly increased paw withdrawal latencies from thermal stimuli compared with pretreatment baselines in the same paw (P < 0.0001) and compared with the contralateral paw without magnet application (P < 0.0001). IV injection of MNPs alone had no significant effect on paw withdrawal latency. Absolute ropivacaine concentrations in ankle tissue, and ankle tissue-to-plasma concentration ratios were higher in the MNP/Ropiv group with 30-minute magnet application compared with MNP/Ropiv group without magnet application (mean ± SEM, 150 ± 10 ng/g vs 105 ± 15 ng/g, respectively, and 6.1 ± 0.8 vs 4.2 ± 0.7, respectively). CONCLUSIONS: The current study establishes proof of principle that it is possible to produce ankle block in the rat by IV injection of MNP/Ropiv complexes and magnet application at the ankle. The results indicate that further study of this approach is warranted.

Regional anesthesia for thoracic surgery: a narrative review of indications and clinical considerations.

Background and Objective: Surgical procedures involving incisions of the chest wall regularly pose challenges for intra- and postoperative analgesia. For many decades, opioids have been widely administered to target both, acute and subsequent chronic incisional pain. Opioids are potent and highly addictive drugs that can provide sufficient pain relief, but simultaneously cause unwanted effects ranging from nausea, vomiting and constipation to respiratory depression, sedation and even death. Multimodal analgesia consists of the administration of two or more medications or analgesia techniques that act by different mechanisms for providing analgesia. Thus, multimodal analgesia aims to improve pain relief while reducing opioid requirements and opioid-related side effects. Regional anesthesia techniques are an important component of this approach. Methods: For this narrative review, authors summarized currently used regional anesthesia techniques and performed an extensive literature search to summarize specific current evidence. For this, related articles from January 1985 to March 2022 were taken from PubMed, Web of Science, Embase and Cochrane Library databases. Terms such as "pectoral nerve blocks", "serratus plane block", "erector spinae plane block" belonging to blocks used in thoracic surgery were searched in different combinations. Key Content and Findings: Potential advantages of regional anesthesia as part of multimodal analgesia regiments are reduced surgical stress response, improved analgesia, reduced opioid consumption, reduced risk of postoperative nausea and vomiting, and early mobilization. Potential disadvantages include the possibility of bleeding related to regional anesthesia procedure (particularly epidural hematoma), dural puncture with subsequent dural headache, systemic hypotension, urine retention, allergic reactions, local anesthetic toxicity, injuries to organs including pneumothorax, and a relatively high failure especially with continuous techniques. Conclusions: This narrative review summarizes regional anesthetic techniques, specific indications, and clinical considerations for patients undergoing thoracic surgery, with evidence from studies performed. However, there is a need for more studies comparing new block methods with standard methods so that clinical applications can increase patient satisfaction.

Genomic loci and candidate genes underlying inflammatory nociception.

Heritable genetic factors contribute significantly to inflammatory nociception. To determine candidate genes underlying inflammatory nociception, the current study used a mouse model of abdominal inflammatory pain. BXD recombinant inbred (RI) mouse strains were administered the intraperitoneal acetic acid test, and genome-wide quantitative trait locus (QTL) mapping was performed on the mean number of abdominal contraction and extension movements in 3 distinct groups of BXD RI mouse strains in 2 separate experiments. Combined mapping results detected 2 QTLs on chromosomes (Chr) 3 and 10 across experiments and groups of mice; an additional sex-specific QTL was detected on Chr 16. The results replicate previous findings of a significant QTL, Nociq2, on distal Chr 10 for formalin-induced inflammatory nociception and will aid in identification of the underlying candidate genes. Comparisons of sensitivity to intraperitoneal acetic acid in BXD RI mouse strains with microarray mRNA transcript expression profiles in specific brain areas detected covarying expression of candidate genes that are also found in the detected QTL confidence intervals. The results indicate that common and distinct genetic mechanisms underlie heritable sensitivity to diverse inflammatory insults, and provide a discrete set of high-priority candidate genes to investigate further in rodents and human association studies. Novel genomic regions linked to inflammatory nociception were detected, a previously reported locus was confirmed, and high-priority candidate genes for inflammatory nociception and pain were identified.