Nerve Block In Rats Research Articles

Ultrasound-guided and ‘blind’ sciatic nerve injection techniques: Comparison in rat cadavers

ObjectiveTo compare the success rate and extent of sciatic nerve staining with a bupivacaine–dye solution using two injection techniques: ‘blind’ or ultrasound-guided approach. Study designProspective, experimental, randomized, cadaveric study. AnimalsAdult female Wistar rat cadavers [n = 24, mass 352 g (323–374)]. MethodsEach sciatic nerve was randomly allocated to one of two groups: ‘blind’ (group B) or ultrasound-guided approach (group US) to injection. Following injection of bupivacaine–dye solution (0.1 mL), gross anatomical dissection was performed to visualize nerve staining, categorizing it as either positive or negative. The length of nerve staining was then measured and visual inspection conducted to identify potential nerve damage. Fisher's exact test was used to compare positive or negative nerve staining, and the Wilcoxon signed rank test used to compare the length of nerve staining between groups. ResultsIn group B, the bupivacaine–dye solution stained 16/24 sciatic nerves (67% success). In group US, staining was successfully observed in all 24 nerves (100% success, p < 0.004). The length of nerve staining [median (interquartile range)] was 2 (2–3) mm in group B and 5 (4–6) mm in group US (p < 0.001). One sciatic nerve in group B had injectate distributed over 16 mm, suggestive of an intraneural injection. No signs of laceration or nerve damage were visible under 6× magnification in either group. Conclusions and clinical relevanceThe ultrasound-guided approach for sciatic nerve injection demonstrated a higher success rate with superior injectate distribution when compared with the ‘blind’ approach. Ultrasound guidance is recommended over a ‘blind’ approach for sciatic nerve block in rats when possible.

The use of granisetron on bupivacaine induced sciatic nerve block in rats

Purpose The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonists on regional anaesthesia are complex and unclear. The present study was designed to test the hypothesis that granisetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor block, sensory block, and proprioception in a dose-dependent fashion in a rat model of bupivacaine-induced sciatic nerve blockade. Materials and methods Thirty-eight male Wistar Albino rats that received unilateral sciatic nerve blocks were randomly divided into five experimental groups. Group B received a perineural of 0.3 ml of bupivacaine alone; Group BG800 received perineural 0.3 ml of bupivacaine and 800 µg of granisetron 10 min later; Group BG1200 received perineural 0.3 ml of bupivacaine and 1200 µg of granisetron 10 min later; Group BG1200IP received a perineural 0.3 ml of bupivacaine and an intraperitoneal injection of 1200 µg of granisetron 10 min later; and Group S was sham operated. A blinded investigator assessed motor, sensory and proprioception function every 10 min until the return of normal function. Results The medians for recovery times in Group B, Group BG800, Group BG1200, and Group BG1200IP were 105, 64, 85, and 120 min for motor function, respectively; 80, 64, 84, and 104 min for sensory function; 80, 63, 85, and 108 min were calculated for the proprioception function. The time to the return of normal motor, sensory, and proprioception function was not statistically significantly different between the groups (p > 0.05). Motor block did not develop in any of the rats in Group S. Conclusions Local and systemic application of granisetron was not significantly decrease the duration of bupivacaine induced motor, sensory, and proprioception block of sciatic nerve in rat.

Retracted: Effect of Ropivacaine-Loaded Magnetic Nanoparticles on Ankle Nerve Block in Rats.

[This retracts the article DOI: 10.1155/2021/8553015.].

Effect of Ropivacaine-Loaded Magnetic Nanoparticles on Ankle Nerve Block in Rats.

Aim Our study is to determine the influence of ropivacaine-loaded magnetic nanoparticles (MNP/Rop) on ankle nerve block in rats. Materials and Methods MNP/Rop was prepared and then injected intravenously into rats to evaluate its anesthetic effect on rat limbs. Mechanical pain thresholds paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWL) were employed for the assessment of ankle nerve block in rats. Results PWT increased from T1 to T4 in each group (P < 0.05). The intergroup comparison determined no distinct difference in the PWT value among the three series at T1 (P > 0.05); however, PWT values at T2-T4 were higher in nerve block control group (NBCG) and MNP/Rop group than in blank group (BG), and they remained slightly higher in MNP/Rop group than in NBCG. The intragroup comparison revealed that from T1 to T4, PWL in each group showed a rising trend. The PWL at T1 showed no evident difference among the three series (P > 0.05); however, PWL values at T2-T4 were higher in NBCG and MNP/Rop group than in BG, and they remained slightly higher in MNP/Rop group than in NBCG. In MNP/Rop group, both PWT and PWL increased with the increase of Fe3O4 load in MNP/Rop (P < 0.05), while PWT and PWL remained unchanged when the load was 2.189%; moreover, PWT and PWL elevated as Rop concentration increased in MNP/Rop (P < 0.05), while they kept unaltered under 40 μL 1% Rop. Conclusion Intravenous injection of MNP/Rop into rats and inhalation of MNP into the ankle joint can effectively block ankle nerve conduction in rats.

Effect of Lidocaine Solid Lipid Nano-particles on Sciatic Nerve Anesthesia Block in Rats

This research aimed at exploring the effect of lidocaine solid lipid nano-particles on sciatic nerve anesthesia block in rats. Firstly, we prepared liposomes encapsulated with lidocaine (nano-lidocaine).Then, we stimulated sciatic nerve of rats injected with narcotic drugs, and evaluated their sensory nerve block and motor nerve block. Finally, we observed their systemic toxic reaction and inflammatory infiltration. We found that compared with rats injected with free lidocaine, the sciatic nerve block time of those injected with nano-lidocaine was longer, and its blocking effect on sensory and motor nerve was stronger than that of those injected with free lidocaine. No systemic toxic reaction was observed in the experimental group. Histological examination manifested that there was mild or moderate inflammatory cell infiltration in the free lidocaine group, while there was no obvious cell infiltration in the nano-lidocaine group. Thus, we believe that lidocaine encapsulated with nano-liposomes has a small particle size, which can produce extra long sciatic nerve block in rats without systemic toxicity and local tissue damage. So, it has satisfactory anesthetic effect and safety.

Effect of magnetic nanoparticles containing ropivacaine on ankle nerve block in rats

Ropivacaine (RVC), a common pain management drug used for clinical anesthesia and postoperative analgesia, inhibits peripheral nociceptive pain stimulation. However, the potential neurological damage resulting from RVC use must be considered. Developing a strategy to enhance the local anesthetic effect of RVC while reducing its potential acute toxicity to the central nervous system is urgently needed. In this study, a novel RVC nanocomposite drug, magnetic iron oxide/polyethylene glycol-carboxymethyl chitosan/ropivacaine nanoparticle (mCMCS-PEG/RVC NPs), was synthesized with magnetic iron oxide. The inherent shell–core structure of mCMCS-PEG retained core magnetic properties, improved the stability and biocompatibility of magnetic nanoparticles, and avoided excessive degradation. Thus, mCMCS-PEG/RVC NPs are expected to provide a new pain management strategy for perioperative patients.

Effects of local dexmedetomidine administration on the neurotoxicity of ropivacaine for sciatic nerve block in rats.

Dexmedetomidine, used as an adjuvant to local anesthetics (LAs), may prolong the duration of peripheral nerve block. However, the effect of dexmedetomidine on the neurotoxicity of LAs is not completely understood. The present study was designed to investigate the efficacy of two doses of dexmedetomidine as an adjuvant to ropivacaine and its protective effect against the neurotoxicity of LAs. Paw withdrawal thermal latency testing was used to detect the sensory blockade. Extensor postural thrust testing was used to detect the motor blockade. The results demonstrated that the addition of dexmedetomidine to ropivacaine prolonged the duration of sensory and motor blockade in a dose-dependent manner compared with ropivacaine alone. TUNEL staining was performed to examine apoptosis. Western blotting was used to detect the Cleaved caspase-3 expression levels. The results showed that the addition of dexmedetomidine to ropivacaine decreased the rate of apoptosis and caspase-3 expression levels in a dose-dependent manner compared with ropivacaine alone (P<0.05). In addition, the rate of apoptosis and caspase-3 expression levels were significantly lower in the high-dose dexmedetomidine group compared with the low-dose dexmedetomidine group (P<0.05). The results suggested that the addition of dexmedetomidine to ropivacaine for sciatic nerve block in rats not only prolonged the duration of sensory and motor block of the sciatic nerve, but also markedly alleviated ropivacaine-induced neurotoxicity by decreasing caspase-3-dependent sciatic nerve cell apoptosis. Furthermore, the present study indicated that dexmedetomidine was more effective at a dose of 20 µg/kg compared with 6 µg/kg.

Reversing Effect of Insulin on Local Anesthetics-Induced Sciatic Nerve Block in Rats.

Background Local anesthetics are used in various purposes from topical and infiltration anesthesia to peripheral nerve or central neural blockade. Even though local anesthetics are relatively safe, they can have some toxic and adverse effects. Prolonged sensory and motor block is another example of an unwanted complication. The primary objective of this study was to determine whether insulin has a reversal effect on the peripheral (sciatic) nerve block with lidocaine or bupivacaine. Methods The surgically exposed sciatic nerves in rats were blocked with lidocaine or bupivacaine, and then 0.1 ml of normal saline or 0.1 ml normal saline containing 0.1 IU a short-acting form of insulin was administrated per body in each group. Before and after sciatic nerve block, as well as until recovery from the nerve block after normal saline or insulin treatment, nerve conduction studies such as monitoring loss and recovery of the waveforms and amplitudes were performed to evaluate the status of motor nerve conduction. Results Complete recovery time of nerve conduction status in lidocaine + normal saline group was 58 ± 16 min, whereas that in lidocaine + insulin group was 17 ± 3 min and the difference was statistically significant (p < 0.01). Complete recovery time of nerve conduction status in bupivacaine + normal saline group was 116 ± 16 min and that in bupivacaine + insulin group was 36 ± 4 min and the two groups were significantly different (p < 0.01). Conclusions Insulin can reverse peripheral nerve block induced by lidocaine or bupivacaine.

Addition of dexmedetomidine to QX-314 enhances the onset and duration of sciatic nerve block in rats.

An experimental set-up was designed to observe whether adding dexmedetomidine to QX-314 would enhance the onset and duration of sensory and motor function in a rat sciatic nerve block model. Fifty-six Sprague-Dawley rats received unilateral sciatic nerve blocks with 0.2 mL of 35 mmol/L QX-314 alone, dexmedetomidine (5.3 μmol/L (1 μg/kg), 26.4 μmol/L (5 μg/kg), 52.8 μmol/L (10 μg/kg)) alone, or a combination of the two. Thermal nociception and motor function were assessed by an investigator blinded to the drug treatment, and sciatic nerves and perineural tissues were harvested at 14 days after injection. In addition, we examined the effects of these solutions on compound action potentials in isolated frog sciatic nerves. Dexmedetomidine added to QX-314 enhanced the onset and duration of thermal nociception block and motor block (P < 0.05) without aggravating histopathological injuries. Furthermore, 52.8 μmol/L dexmedetomidine added to 35 mmol/L QX-314 showed less inflammation than QX-314 alone at 14 days (P = 0.003). Dexmedetomidine plus QX-314 was shown to dose-dependently reduce the compound action potentials relative to QX-314 alone (P < 0.05). It was concluded that co-administration of QX-314 with a clinical dose of dexmedetomidine produced a synergistic anesthetic effect to enhance the effect of sciatic nerve block.

The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats.

ObjectiveThe quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination.MethodsQX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine.Results0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks.ConclusionThe combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment.

The effects of bupivacaine combined with different adjuvants on block onset and duration and on ion channel expressions (SCN9A, TRPM) in sciatic nerve block in rats.

The objective of this experimental study was to examine the effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to bupivacaine on block onset and effect times, as well as the effects on the Na+ and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic nerve cell membrane. Rats were divided into five groups: Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine + dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine + epinephrine. For each group, 0.2 mL of local anesthetic was injected into the sciatic nerve bifurcation point of the right leg. Sensory (proprioceptive and nociceptive block) and motor block onset and ending times were recorded. The shortest onset time for the examined sciatic block was observed in the BC group, whereas the longest sensory and motor block times were observed in the BD group. The present data suggest suppressed TRPM7 and increased TRPM2 in the groups other than the BE group. Clonidine is more suitable for fast onset of peripheral nerve blocks, whereas the addition of dexmedetomidine is better in terms of duration. Because the SCN9A and TRPM2,4,7 expression ratios of the BE group showed the least amount of change, this group had the best cellular integrity.

Optimal Effect of Phenol Block in the Sciatic Nerve of Rats: Standardization of Minimized Dosage and Duration of Application.

The phenol nerve block has been widely used in clinical practice for spasticity reduction, but the correlation between the dosage of phenol and its effectiveness has seldom been discussed. The objective was to determine the optimal duration of phenol in contact with the nervous tissue and to investigate the dose-response relationship of 5% aqueous phenol solution by percutaneous nerve block in rats. Group I (n = 8) received sciatic nerve block by bathing the nerves in phenol solution, and group II (n = 40) by injecting phenol percutaneously. Group IIa to IId received different volumes (0.80, 0.16, 0.08 and 0.04 ml) and group IIe received normal saline. Compound muscle action potential (CMAP) was measured pre-injection and at 90 and 270 sec after injection and after surgical exposure of the nerves. The duration of CMAP reduced by 10%, 25%, 50%, 75% and 100% after phenol injection was also recorded. The mean latency for the evoked response to subside in direct phenol application (group I) and percutaneous nerve block (group IIa) were 73.5 ± 5.9 and 62.4 ± 7.6 sec, respectively. There was no statistical difference for the time periods in the blocking effect elicited by phenol solution between these two methods. Ninety sec was set as the optimal duration for phenol to produce complete conduction blockage. Higher volume of phenol produced more significant blocking effect at 90 and 270 sec after injection. Percutaneous injection with 0.16 ml of phenol solution had the same blocking effect as 0.8 ml. The continuous injection model for percutaneous phenol block indeed used significantly more phenol than actually needed. Clinically, the progressive injection model can be used to minimize injection volume.

Anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin for dental anaesthesia after inferior alveolar nerve block in rats

Bupivacaine is a long-acting local anaesthetic that is widely used in medicine and dentistry. The duration and intensity of its sensory blockade in animal models is increased by its inclusion in complexes with cyclodextrins. The aim of the present study was to evaluate the anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex for dental anaesthesia after inferior alveolar nerve block in rats. Thirty rats were each given an injection close to the mandibular foramen of 0.2ml of one of the following formulations: 0.5% bupivacaine alone; 0.5% bupivacaine with 1:200,000 epinephrine; and 0.5% bupivacaine-HPβCD inclusion complex (bupivacaine-HPβCD). The other sides were used as controls, with either 0.9% saline or anaesthetic-free HPβCD solution being injected. The onset, success, and duration of pulpal anaesthesia were assessed by electrical stimulation (“pulp tester”) on inferior molars. Results were analysed using ANOVA (Tukey), log rank, and chi square tests (α=5%). There were no differences among the formulations in onset of anaesthesia (p=0.59) or between the bupivacaine plus epinephrine and bupivacaine plus HPβCD in duration of anaesthesia, but bupivacaine plus epinephrine gave significantly higher values than bupivacaine alone (p=0.007). Bupivacaine plus epinephrine was a better anaesthetic than bupivacaine alone (p=0.02), while Bupi-HPβCD gave intermediate results, and therefore did not differ significantly from the other 2 groups (p=0.18 with bupivacaine alone; and p=0.44 with bupivacaine plus epinephrine). The bupivacaine-HPβCD complex showed similar anaesthetic properties to those of bupivacaine with epinephrine.

Effects of Perineural Administration of Dexmedetomidine in Combination with Levobupivacaine in a Rat Sciatic Nerve Block

ObjectiveThe aim of this study was to assess if perineural administration of dexmedetomidine combined with levobupivacaine increases the duration of the sensory and motor blockade of a sciatic peripheral nerve block in rats. MethodsForty male Sprague–Dawley rats were randomly divided into 5 experimental groups: Group 1, sham; Group 2, perineural levobupivacaine (0.2 mL of a 0.5% solution) and subcutaneous saline; Group 3, perineural levobupivacaine (0.2 mL of a 0.5% solution) plus dexmedetomidine (20 µg/kg dexmedetomidine) and subcutaneous saline; Group 4, perineural saline and subcutaneous dexmedetomidine; and Group 5, perineural saline and subcutaneous saline. Pain reflexes in response to a thermal stimulus were measured at 0 and 240 minutes after drug administration by using a hot-plate and tail-flick tests. Neurobehavioral status, including sensory and motor functions, was assessed by an investigator who was blinded to the experimental groups every 30 minutes until normal functioning resumed. ResultsThe sensory and motor blockades of the rats did not increase in the treatment with dexmedetomidine plus levobupivacaine when compared with the treatment with levobupivacaine alone at all the time points (P > 0.05). Compared with rats in Group 2, those in Group 3 showed significantly higher latency times at 30 and 60 minutes in the hot plate test (P < 0.01). At 30 and 60 minutes, the latency times of the rats in Group 3 were longer than those in Group 2 in the tail-flick test (P < 0.01). Furthermore, the durations of the complete sensory and motor blockade were similar when treatment with levobupivacaine plus dexmedetomidine was compared with treatment with levobupivacaine alone. ConclusionsA 20µg/kg dose of dexmedetomidine added to levobupivacaine did not increase the duration of the sensory and motor blockades in rats. However, treatment with dexmedetomidine plus levobupivacaine increased the quality of analgesia in rats.

Thermal Hyperalgesia After Sciatic Nerve Block in Rat Is Transient and Clinically Insignificant

Ropivacaine has been associated with transient heat hyperalgesia in sciatic nerve blocks in rat. The goal of the present study was to evaluate the hypothesized presence of transient heat hyperalgesia after perineural injection of ropivacaine with a secondary subanalysis of 2 published studies. Paw withdrawal latency was used to assess the duration of sensory blockade and presence of heat hyperalgesia at 210, 240, 270, and 300 minutes and 24 hours after injection. The analysis revealed hyperalgesia at a single time point (240 minutes after injection; mean difference, -0.60 seconds; P = 0.012) that resolved within 30 minutes, and there was no other significant hyperalgesia at other time points. Although statistically significant, the single time point measurement represented only an 11% change from baseline and was no longer present 30 minutes later. These data support the need for a reevaluation of the interpretation that pain can be worsened by perineural ropivacaine injection.

Assessing the Use of 50% Enantiomeric Excess Bupivacaine-Loaded Microspheres after Sciatic Nerve Block in Rats

To achieve better therapeutic benefits of local anesthetics in the control of postoperative pain through controlled-release carrier. The objective of this study was to compare the characteristics of sensory and motor blockade between microspheres without local anesthetic: racemic bupivacaine-loaded microspheres; 50% enantiomeric excess bupivacaine-loaded microspheres; and free 50% enantiomeric excess bupivacaine. Wistar rats were distributed into four groups: A (Microsphere); B (S50-R50 bupivacaine-loaded microsphere); C (50% enantiomeric excess bupivacaine-loaded microsphere); and D (50% enantiomeric excess bupivacaine). Inhalation anesthesia was performed before the sciatic nerve block (2% halothane and 100% O(2)). Sensorial blockade was measured by the time required for each rat to withdraw its paw from a hot plate at 56°C (positive>4 sec). Motor blockade was measured by the time between drug injection until recovery of a motor score of 2 on the established criterion. The sensory response was significantly more frequent in groups B, C, and D than in group A (p<0.001). There were no statistically significant differences in the response to the sensory test in groups B, C, and D (p>0.05). The response to the motor test was also significantly more frequent in groups B, C, and D than in group A (p=0.02). A tendency to greater positivity in the motor test was more frequently found in groups B and D than in group C (p=0.10). Controlled-release of 50% enantiomeric excess bupivacaine-loaded microspheres showed similar results regarding analgesia and less motor blockade when compared to other anesthetic formulations.

Perineural Dexmedetomidine Added to Ropivacaine for Sciatic Nerve Block in Rats Prolongs the Duration of Analgesia by Blocking the Hyperpolarization-activated Cation Current

The current study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (I(h)) current. In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 μM or 6 μg/kg) were assessed with or without the pretreatment of α(1)- and α(2)-adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the I(h) current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min postblock. The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (I(h) current blocker) compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90-180 min (P < 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 μM) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect. Dexmedetomidine added to ropivacaine caused approximately a 75% increase in the duration of analgesia, which was reversed by pretreatment with an I(h) current enhancer. The analgesic effect of dexmedetomidine was not reversed by an α(2)-adrenoceptor antagonist.

Perineural Dexmedetomidine Provides an Increased Duration of Analgesia to a Thermal Stimulus When Compared With a Systemic Control in a Rat Sciatic Nerve Block

The present study was designed to test the hypothesis that perineural dexmedetomidine provides a longer duration of analgesia than the same dose given subcutaneously in a peripheral nerve block in rats. Fifty-four rats received unilateral sciatic nerve blocks along with a subcutaneous injection at the base of the neck by a blinded investigator assigned at random. Combinations were as follows: perineural ropivacaine alone and subcutaneous (SQ) saline, perineural ropivacaine plus dexmedetomidine and SQ saline, perineural ropivacaine and SQ dexmedetomidine, perineural dexmedetomidine alone and SQ saline, and perineural saline and SQ dexmedetomidine. The ropivacaine concentration was fixed at 0.5%, and the dose of dexmedetomidine was 20.0 microg/kg (119.3 micromol/L). Sensory analgesia was assessed by paw withdrawal latency (PWL) to a thermal stimulus every 30 mins after the block for a minimum of 240 mins or until the return of normal sensory function. The unblocked paw served as the control for assessment of systemic, centrally mediated analgesia. Between-group and within-group comparisons of PWL were obtained for measures from operative and control paws. The analgesic effect of perineural dexmedetomidine was superior to that of subcutaneous dexmedetomidine in ropivacaine sciatic nerve blocks from time points 120 to 210 mins (P < 0.017). Perineural dexmedetomidine also showed less systemic effect as measured by the unblocked control paw at multiple time points (P < 0.05). Perineural dexmedetomidine alone provided a brief, partial sensory block. Sensory analgesia provided by dexmedetomidine added to ropivacaine for peripheral nerve blocks in rat is a peripherally mediated effect.

Age-dependent Bupivacaine-induced Muscle Toxicity during Continuous Peripheral Nerve Block in Rats

Regional blocks improve postoperative analgesia and postoperative rehabilitation in children and adult patients. Continuous peripheral nerve blocks have been proposed as safe and effective techniques for postoperative pain relief and chronic pain therapy, particularly in small children. Few clinical reports have described myotoxicity induced by bupivacaine in these young patients, in contrast with a larger number of observations in adults. Here, the authors addressed this issue by a comparative evaluation of bupivacaine-induced myotoxicity in young versus adult rats. Femoral nerve block catheters were inserted in male Wistar rats. Young (3-week-old) and adult (12-week-old) rats were randomly assigned to received seven injections (1 ml/kg) of 0.25% bupivacaine (n = 6 per experiment) or isotonic saline (n = 6 per experiment) at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle adjacent to the femoral nerve was quickly dissected. Oxygen consumption rates were measured in saponin-skinned fibers, mitochondrial adenosine triphosphate synthesis rates were determined by bioluminescence, and citrate synthase activity was determined by spectrophotometry. Muscle ultrastructural damage was also examined and scored as normal, focal disruption, moderate disruption, or extreme disruption of the sarcomeres. Bupivacaine caused a reduction of mitochondrial adenosine triphosphate synthesis rate, a decrease of citrate synthase activity, and muscle ultrastructural damages. Young rats treated with bupivacaine showed more severe alterations of mitochondrial bioenergetics and muscle ultrastructure. These findings demonstrate that bupivacaine-induced myotoxicity can be explained by mitochondrial bioenergetics alterations, which are more severe in young rats.

Perineural Dexmedetomidine Added to Ropivacaine Causes a Dose-dependent Increase in the Duration of Thermal Antinociception in Sciatic Nerve Block in Rat

The current study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would increase the duration of antinociception to a thermal stimulus in a dose-dependent fashion in a rat model of sciatic nerve blockade. Fifty adult Sprague-Dawley rats (10 rats/group) received unilateral sciatic nerve blocks with 0.2 ml ropivacaine (0.5%) or 0.2 ml ropivacaine (0.5%) plus dexmedetomidine (2.7 microm [0.5 microg/kg], 11.7 microm [2 microg/kg], 34.1 microm [6 microg/kg], or 120.6 microm [20 microg/kg]) in a randomized, blinded fashion. Time to paw withdrawal latency to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline. Dexmedetomidine added to ropivacaine increased the duration of dense sensory blockade and time for return to normal sensory function in a dose-dependent fashion (P < 0.005). There was a significant time (P < 0.005), dose (P < 0.005), and time-by-dose effect (P < 0.005) on paw withdrawal latencies of the operative paws. There were no significant differences in paw withdrawal latencies of the control paws, indicating little systemic effect of the dexmedetomidine. The duration of motor blockade was also increased with dexmedetomidine. High-dose dexmedetomidine (120.6 mum) was not neurotoxic. This is the first study showing that dexmedetomidine added to ropivacaine increases the duration of sensory blockade in a dose-dependent fashion in rats. The findings are an essential first step encouraging future efficacy studies in humans.