| This thesis is dedicated to the pharmacology & therapeutics of local anesthetics, with a specific focus on their analgesic properties.; The specific objective of the laboratory studies was to define the concentration-dependent effects of lidocaine on the membrane properties and excitability of neurons in the ventral posterior lateral thalamic nucleus (VPL), a major somatosensory and nociceptive relay station that plays a central role in pain states. Lidocaine produces central analgesia and sedation when present in the systemic circulation at low concentrations, and evidence implicates VPL neurons in these actions. Differential interference contrast infrared (DIC-IR) videomicroscopy-guided whole-cell patch clamp techniques were used to record from VPL neurons in rat brain slice preparations. Low, analgesic lidocaine concentrations (10 muM) significantly decreased neuronal input resistance (R i), which shunted action potentials, increased current thresholds, and reduced tonic firing. The effects were not associated with the classic signs of Na+ conductance blockade. The GABAA receptor antagonist, bicuculline, had no effect on the lidocaine-induced shunt. Higher lidocaine concentrations (≥300 muM; clinically CNS-toxic) did not decrease Ri but reversibly unmasked high threshold Ca2+ spikes (HTSs), susceptible to blockade by Cd2+. Extracellular QX-314, a quaternary lidocaine analogue, increased rather than decreased Ri. Similarly, neither procainamide nor bupivacaine reduced Ri. In summary, these studies identified novel actions of lidocaine in the thalamus, distinct from the classic effects on Na + conductance. The observation of an unmasking of high threshold Ca 2+ spikes is in contrast to previous studies in other tissues showing that lidocaine blocks Ca2+ conductances, and is of potential significance for the mechanisms of local anesthetic CNS toxicity.; The purpose of the clinical studies was to test if postoperative pain control in patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR) under general anesthesia is improved by addition of a preincisional femoral 3-in-1 block with ropivacaine 0.2% to standard intra-articular instillation at the end of surgery. In a prospective, randomized, controlled, double-blind trial (RCT), 44 patients scheduled for inpatient ACLR were studied. In conclusion, the clinical studies demonstrated no significant effect in an RCT of a femoral 3-in-1 block with ropivacaine 0.2% on postoperative analgesic consumption, compared to intra-articular instillation alone, in patients undergoing ACLR under general anesthesia. (Abstract shortened by UMI.)... |
