This article provides a brief overview of earlier work of our group on the peripheral signaling of pain, summarizes more recent studies on the role of opioids in chronic neuropathic pain, and speculates on the future of gene-based therapies as novel strategies to enhance the peripheral modulation of pain. Neurophysiological and psychophysical studies have revealed features of primary afferent activity from somatic tissue that led to improved understanding of the physiology and pathophysiology of pain signaling by nociceptive and non-nociceptive fibers. The demonstration of peripheral opioid mechanisms in neuropathic pain suggests a potential role for these receptors in the modulation of pain at its initiation site. Our work has focused on characterizing this peripheral opioid analgesia in chronic neuropathic pain such that it can be exploited to develop novel and potent peripheral analgesics for its treatment. Ongoing research on virus-mediated gene transfer strategies to enhance peripheral opioid analgesia is presented.

Background and Objectives

Research in the field of anesthesiology relies heavily on longitudinal designs for answering questions about long-term efficacy and safety of various anesthetic and pain regimens. Yet, anesthesiology research is lagging in the use of advanced statistical methods for analyzing longitudinal data. The goal of this paper is to increase awareness of the advantages of modern statistical methods and promote their use in anesthesia research.

Methods

Here we introduce 2 modern and advanced statistical methods for analyzing longitudinal data: the generalized estimating equations (GEE) and mixed effects models (MEM). These methods are compared to the conventional repeated measures ANOVA (RM-ANOVA) through a clinical example with 2 types of endpoints (continuous and binary). In addition, we compare GEE and MEM to RM-ANOVA through a simulation study with varying sample sizes, varying number of repeated measures, and scenarios with and without missing data.

Results

In the clinical study, the 3 methods are found to be similar in terms of statistical estimation, while the parameter interpretations are somewhat different. The simulation study shows that the methods of GEE and MEM are more efficient in that they are able to achieve higher power with smaller sample size or lower number of repeated measurements in both complete and missing data scenarios.

Conclusions

Based on their advantages over RM-ANOVA, GEE and MEM should be strongly considered for the analysis of longitudinal data. In particular, GEE should be utilized to explore overall average effects, and MEM should be employed when subject-specific effects (in addition to overall average effects) are of primary interest.

Background

Peripheral nerve blocks (PNB’s) with local anesthetics (LA’s) are commonly performed to provide surgical anesthesia or postoperative analgesia. Nerve injury resulting in persistent numbness or weakness is a potentially serious complication. LA’s have previously been shown to damage neuronal and Schwann cells via several mechanisms. We sought to test the hypothesis that LA’s are toxic to Schwann cells and that the degree of toxicity is directly related to the concentration of LA and duration of exposure. Intraneural injection of LA’s has been shown to produce nerve injury. We sought to test the hypothesis that a prolonged extraneural infusion of LA can also produce injury.

Materials and Methods

Schwann cells cultured from neonatal rat sciatic nerves were incubated with LA’s at different concentrations (10, 100, 500 and 1000 μM), and each concentration was assessed for toxicity after 4, 24, 48 and 72 hours of exposure. LA’s tested were lidocaine, mepivacaine, chloroprocaine, ropivacaine and bupivacaine. Cell death was assessed by LDH release measured by optical density.

In a separate experiment, a microcatheter was placed along the sciatic nerves of Sprague-Dawley rats. Rats were randomly assigned to receive either 0.9% saline (n = 8) or bupivacaine (0.5% n = 4, 0.75% n = 4) via the perineural catheters for 72 hours. The rats were then euthanized and their nerves sectioned and stained for analysis. Sections were stained for myelin and with an anti-macrophage (CD68) antibody.

Results

None of the LA’s tested produced significant Schwann cell death at very low concentrations (10mM, or 0.0003%) even after prolonged exposure. With prolonged exposure (48 or 72 hours) to high concentrations (1000 μM, o r 0.03%), all of the LA’s tested produced significant Schwann cell death (increased LDH release relative to control as measured by optical density 0.384–0.974, all p-values < 0.001). Only bupivacaine produced significant cell death (0.482, p < 0.001) after prolonged exposure to low concentrations (100 μM, or 0.003%). At intermediate concentrations (500 μM, or 0.015%), cell death was more widespread with bupivacaine (0.768, p < 0.001) and ropivacaine (0.675, p < 0.001) than the other agents (0.204–0.368, all p-values < 0.001).

Prolonged extraneural exposure of rat sciatic nerves to bupivacaine caused significant demyelination and infiltration of nerves with inflammatory cells.

Conclusions

LA’s induce Schwann cell death in a time and concentration-dependent manner. Bupivacaine and ropivacaine have greater toxicity at intermediate concentrations, and prolonged exposure to bupivacaine produces significant toxicity even at low concentrations. Brief exposure to high concentrations of bupivacaine damages Schwann cells. Prolonged extraneural infusion of bupivacaine results in nerve injury.

Background

Analyses of existing nationally representative information on how changes in ambulatory orthopedic surgery have affected anesthesia practice over time are rare. We sought to characterize temporal changes in factors surrounding ambulatory orthopedic surgery and anesthesia.

Methods

Data from the National Survey of Ambulatory Surgery for the years of 1996 and 2006 were analyzed. Entries indicating the performance of knee ligamentoplasty, meniscectomy or shoulder arthroscopy were identified and included in the sample. Temporal changes in a number of variables associated with orthopedic ambulatory surgery were assessed, including: 1) the number of procedures being performed, 2) patient and health care system related demographics and 3) anesthesia related variables.

Results

Nationwide, the total number of ligamentoplasties, meniscectomies and shoulder arthroscopies increased from 1996 to 2006 by 66% (N=258,932 to N=428,712), 51% (N=456,698 to N=690,164), and 349% (N=93,105 to N=418,188) respectively (P<0.0001). Between 1996 and 2006 the use of peripheral nerve blocks increased from 0.6% to 9.8% for meniscectomies (P<0.0001), from 1.5% to 13.7% for ligamentoplasties (P<0.0001), and from 11.5% to 23.9% for shoulder arthroscopies (P<0.0001), respectively. Neuraxial anesthesia utilization fell from 11.8% to 6.3% for meniscectomies (P<0.0001) and 13.6% to 7.3% for ligamentoplasties (P<0.0001) from 1996 to 2006, respectively.

Conclusion

Substantial increases in the number of ambulatory knee and shoulder procedures occurred over time, relating to increased demand for anesthesia providers in this field. Trends towards increased use of peripheral nerve blocks may have to be considered by educators when preparing residents for practice.

Background

Preliminary studies using perineural sciatic ropivacaine in rat demonstrated unexpected heat hyperalgesia after block resolution. To better characterize the time course relative to mechanical anesthesia-analgesia, we tested the hypothesis that ropivacaine 0.5% leads to transient heat hyperalgesia in rat independent of mechanical nociception. We also evaluated functional toxicity (e.g., long-term hyperalgesia and/or tactile allodynia 2 weeks post-injection).

Methods

Under surgical exposure, left sciatic nerve block was performed in 2 groups of adult male rats – ropivacaine (200 μL, 5 mg/mL, n=14) versus vehicle (n=11). The efficacy and duration of block was assessed with serial heat, mechanical (Randall-Selitto testing), and tactile (von Frey-like monofilaments) tests; motor-proprioceptive (rotarod) and sedation tests were employed 1 hr and 7 hr post-injection. The presence of nerve injury was assessed by repeating the heat, tactile, and motor tests 12–14 days post-injection.

Results

Ropivacaine-induced anesthesia was fully manifest at 1 hr post-injection. At 3 hr post-injection, heat hypersensitivity was present in the setting of resolved mechanical analgesia. All behavioral measures returned to baseline by 2 wk post-injection. There was no evidence of (i) behavioral sedation, (ii) persistent changes in heat or mechanical sensitivity, or (iii) persistent changes in proprioceptive-motor function at 12–14 days post-injection.

Conclusions

Ropivacaine 0.5% induces transient heat hyperalgesia in the setting of resolved mechanical analgesia, further suggestive of modality and/or nociceptive fiber specificity. Whether this finding partially translates to “rebound pain” after patients’ nerve blocks wear off requires further study.

Background

When using ultrasound guidance to place a perineural catheter for a continuous peripheral nerve block, keeping the needle-in plane and nerve in short-axis results in a perpendicular needle-to-nerve orientation. Many have opined that when placing a perineural catheter via the needle, the acute angle may result in the catheter bypassing the target nerve when advanced beyond the needle tip. Theoretically, greater catheter tip-to-nerve distances result in less local anesthetic-to-nerve contact during the subsequent perineural infusion, leading to inferior analgesia. While a potential solution may appear obvious—advancing the catheter tip only to the tip of the needle, leaving the catheter tip at the target nerve—this technique has not been prospectively evaluated. We therefore hypothesized that during needle in-plane ultrasound-guided perineural catheter placement, inserting the catheter a minimum distance (0-1 cm) past the needle tip is associated with improved postoperative analgesia compared with inserting the catheter a more-traditional 5-6 cm past the needle tip.

Methods

Preoperatively, subjects received a popliteal-sciatic perineural catheter for foot or ankle surgery using ultrasound guidance exclusively. Subjects were randomly assigned to have a single-orifice, flexible catheter inserted either 0-1 (n=50) or 5-6 cm (n=50) past the needle tip. All subjects received a single-injection mepivacaine (40 mL of 1.5% with epinephrine) nerve block via the needle, followed by catheter insertion and a ropivacaine 0.2% infusion (basal 6 mL/h, bolus 4 mL, 30 min lockout), through at least the day following surgery. The primary end point was average surgical pain as measured with a 0-10 numeric rating scale the day following surgery. Secondary end points included time for catheter insertion, incidence of catheter dislodgement, maximum (“worst”) pain scores, opioid requirements, fluid leakage at the catheter site, and the subjective degree of an insensate extremity.

Results

Average pain scores the day following surgery for subjects of the 0-1 cm group was a median (interquartile) of 2.5 (0.0-5.0), compared with 2.0 (0.0-4.0) for subjects of the 5-6 cm group (p=0.42). Similarly, among the secondary end points, no statistically significant differences were found between the two treatment groups. There was a trend of more catheter dislodgements in the minimum-insertion group (5 vs. 1; p=0.20).

Conclusions

This study did not find evidence to support the hypothesis that for popliteal-sciatic perineural catheters placed using ultrasound guidance and a needle in-plane technique, inserting the catheter a minimum distance (0-1 cm) past the needle tip improves (or worsens) postoperative analgesia compared with inserting the catheter a more-traditional distance (5-6 cm). Caution is warranted if extrapolating these results to other catheter designs, ultrasound approaches, or anatomic insertion sites.

Background and Objectives

Clonidine, buprenorphine, dexamethasone, and midazolam (C,B,D,M) have been used to prolong perineural local anesthesia in the absence of data on the influence of these adjuvants on local anesthetic (LA)-induced neurotoxicity. Therefore, the impact of these adjuvants on ropivacaine (R)-induced death of isolated sensory neurons was assessed.

Methods

The trypan blue exclusion assay was used to assess death of sensory neurons isolated from adult male Sprague-Dawley rats. Drugs were applied, alone or in combination, for 2 or 24 hrs at 37°C.

Results

Neuronal viability was halved by 24 hr exposure to R (2.5 mg/mL), far exceeding the neurotoxicity of C, B, D, or M (at 2–100 times estimated clinical concentrations). Plain M at twice the estimated clinical concentration produced a small but significant increase in neurotoxicity at 24 hr. After 2 hr exposure, high concentrations of B, C, and M increased the neurotoxicity of R; the combination of R+M killed over 90% of neurons. Estimated clinical concentrations of C+B (plus 66 µg/mL D) had no influence on (i) R-induced neurotoxicity, (ii) the increased neurotoxicity associated with the combination of R+M, or (iii) the neurotoxicity associated with estimated clinical concentrations of M. There was dose-response neurotoxicity with 133 µg/mL D combined with R+C+B

Conclusions

Results with R re-affirm the need to identify ways to mitigate LA-induced neurotoxicity. While having no protective effect on R-induced neurotoxicity in vitro, future research with adjuvants should address if the C+B+D combination can enable reducing R concentrations needed to achieve equi-analgesia (and/or provide equal or superior duration, in preclinical in vivo models).

Background

Previously, we have demonstrated that extending a continuous femoral nerve block from overnight to four days following total knee arthroplasty provides clear benefits during the infusion, but not subsequent to catheter removal. However, there were major limitations in generalizing the results of that investigation, and we subsequently performed a very similar study using a multicenter format, with many healthcare providers, in patients on general orthopedic wards; thus, greatly improving inference of the results to the general population. Not surprisingly, the perioperative/short-term outcomes differed greatly from the first, more-limited, study. We now present a prospective follow-up study of the previously published, multicenter, randomized, controlled clinical trial to investigate the possibility that an extended ambulatory continuous femoral nerve block decreases long-term pain, stiffness, and functional disability following total knee arthroplasty; which greatly improves inference of the results to the general population.

Methods

Subjects undergoing total knee arthroplasty received a continuous femoral nerve block with ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to either continue perineural ropivacaine (n=28) or normal saline (n=26). Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative day 4. Health-related quality-of-life was measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index preoperatively and then at 7 days, as well as 1, 2, 3, 6, and 12 months following surgery. This index evaluates pain, stiffness, and physical functional disability. For inclusion in the analysis, we required a minimum of four of the six time points, including day 7 and at least two of months 3, 6, and 12.

Results

The two treatment groups had similar WOMAC scores for the mean area under the curve calculations (point estimate for the difference in mean area under the curve for the two groups [overnight infusion group – extended infusion group]=3.8, 95% confidence interval: −3.8 to +11.3; p=0.32) and at all individual time points (p>0.05).

Conclusions

This investigation found no evidence that extending an overnight continuous femoral nerve block to four days improves (or worsens) subsequent pain, stiffness, or physical function following TKA in patients of multiple centers convalescing on general orthopedic wards.

BACKGROUND AND OBJECTIVES

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG

METHODS

Male Sprague–Dawley rats were divided into four groups: SNL (tight ligation and transection of spinal nerves) or normal, with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) in DRG, and CD11B antibody (OX-42) in spinal cord.

RESULTS

Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL.

CONCLUSION

A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rational for the clinical use of localized steroid injections clinically, and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

Background and Objectives

The transient and rarely clinically relevant effect of bone and cement embolization during unilateral joint arthroplasty is a known phenomenon. However, available studies do not address events surrounding bilateral total hip arthroplasties, during which embolic load is presumably doubled. To elucidate events surrounding this increasingly utilized procedure and assess the effect on the pulmonary hemodynamics in the intra- and postoperative period, we studied 24 subjects undergoing cemented bilateral total hip arthroplasty during the same anesthetic session.

Materials

Twenty four patients without previous pulmonary history undergoing cemented bilateral total hip arthroplasty under controlled epidural hypotension were enrolled. Pulmonary artery catheters were inserted and hemodynamic variables were recorded at baseline, 5 minutes after the implantation of each hip joint, 1 hour and 1 day postoperatively. Mixed venous blood gases and complete blood counts were analyzed at every time point.

Results

An increase in pulmonary vascular resistance was observed after the second but not the first hip implantation when compared to values at incision. Pulmonary vascular resistance remained elevated 1 hour postoperatively. Pulmonary artery pressures were significantly elevated on post operative day 1 compared to baseline values. The white blood cell count increased in response to the second hip implantation but not the first compared to incision.

Conclusion

The embolization of material during bilateral total hip arthroplasty is associated with prolonged increases in pulmonary artery pressures and vascular resistance, particularly after the second side. The performance of bilateral procedures should be cautiously considered in patients with diseases suggesting decreased right ventricular reserve.

Background

Despite attention to technical details in performance of regional anesthetics, damage to nerves continues to be a concern. Understanding of pathophysiological mechanisms may aid in decreasing the incidence and severity of such injuries.

Methods

Studies from both clinical and basic science perspective are reviewed.

Results

Exposure of peripheral nerves to local anesthetics may result in axonal damage, particularly if the solution is injected intrafascicularly, if the concentration is high, and if duration of exposure is prolonged. Disruption of numerous cellular functions may contribute to neuronal damage by local anesthetics, but elevated intracellular calcium levels may play a central role. Needle penetration of a nerve results in minimal lasting damage unless this is combined with local anesthetic administration within the nerve fascicle. Direct compression by a pronged tourniquet application may damage axons particularly of large myelinated fibers. Ischemia may also contribute to neuronal injury in proportion to the duration of blood flow interruption.

Conclusions

The relative importance of these pathogenic factors in cases of nerve injury after regional anesthesia is not resolved.

Neurologic complications associated with regional anesthesia and pain medicine practice are extremely rare. The ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine addresses the etiology, differential diagnosis, prevention, and treatment of these complications. This Advisory does not focus on hemorrhagic and infectious complications, because they have been addressed by other recent ASRA Practice Advisories. The current Practice Advisory offers recommendations to aid in the understanding and potential limitation of neurologic complications that may arise during the practice of regional anesthesia and pain medicine.

Brachial plexus blockade is the cornerstone of the peripheral nerve regional anesthesia practice of most anesthesiologists. As part of the American Society of Regional Anesthesia and Pain Medicine’s commitment to providing intensive evidence-based education related to regional anesthesia and analgesia, this article is a complete update of our 2002 comprehensive review of upper extremity anesthesia. The text of the review focuses on (1) pertinent anatomy, (2) approaches to the brachial plexus and techniques that optimize block quality, (4) local anesthetic and adjuvant pharmacology, (5) complications, (6) perioperative issues, and (6) challenges for future research.

Background and Objectives

The posterior approach to the brachial plexus—or cervical paravertebral block—has advantages over the anterolateral interscalene approach, but concerns regarding “blind” needle placement near the neuraxis have limited the acceptance of this useful technique. We present a technique to place an interscalene perineural catheter that potentially decreases neuraxial involvement with the use of ultrasound guidance.

Methods

A 55-year-old man scheduled for total shoulder arthroplasty underwent placement of an interscalene perineural catheter. The posterior approach was selected to avoid the external jugular vein and anticipated sterile surgical field. Under in-plane ultrasound guidance, a 17-gauge insulated Tuohy-tip needle was inserted between the levator scapulae and trapezius muscles, and guided through the middle scalene muscle, remaining less than 2 cm below the skin throughout. Deltoid and biceps contractions were elicited at a current of 0.6 mA, and a 19-gauge stimulating catheter was advanced 5 cm beyond the needle tip, without a concomitant decrease in motor response.

Results

The initial 40 mL 0.5% ropivacaine bolus via the catheter resulted in unilateral anesthesia typical of an interscalene block; and subsequent perineural infusion of 0.2% ropivacaine was delivered via portable infusion pump through postoperative day 4.

Conclusions

Continuous interscalene block using an ultrasound-guided posterior approach is an alternative technique that retains the benefits of posterior catheter insertion, but potentially reduces the risk of complications that may result from blind needle insertion.

Background and Objectives:

It is currently unknown if the primary determinant of continuous peripheral nerve block effects is simply total drug dose, or whether local anesthetic concentration and/or volume have an influence. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates—but at an equal total basal dose—produces similar effects when used in a continuous interscalene nerve block.

Methods:

Preoperatively, an interscalene perineural catheter was inserted using the anteriolateral approach in patients undergoing moderately painful shoulder surgery. Subjects were randomly assigned to receive a postoperative perineural infusion of either 0.2% ropivacaine (basal 8 mL/h, bolus 4 mL) or 0.4% ropivacaine (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Our primary end point was the incidence of an insensate hand/finger during the 24-hours beginning the morning following surgery.

Results:

The incidence of an insensate hand/finger did not differ between the treatment groups (n=50) to a statistically significant degree (0.2% ropivacaine mean [SD] of 0.8 [1.3] times; 0.4% ropivacaine mean 0.3 [0.6] times; estimated difference=0.5 episodes, 95% confidence interval, −0.1 to 1.1 episodes; p=0.080). However, this is statistically inconclusive given the confidence interval. In contrast, pain (p=0.020) and dissatisfaction (p=0.011) were greater in patients given 0.4% ropivacaine.

Conclusions:

For continuous interscalene nerve blocks, the 95% confidence interval (plausible differences in the incidence of an insensate hand/finger) contains values ranging from a clinically important disadvantage (1.1) to a clinically unimportant advantage (−0.1) for the lower concentration. Given the statistically inconclusive results and design limitations of the current study, further research on this issue is warranted. In contrast, providing a lower concentration of local anesthetic at a higher basal rate provided superior analgesia. These relationships are different than previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.

Background and Objectives

Previous studies have concluded that transforaminal epidural steroid injections (ESIs) are more effective than interlaminar injections in the treatment of radiculopathies due to lumbar intervertebral disk herniation. There are no published studies examining the depth of epidural space using a transforaminal approach. We investigated the relationship between body mass index (BMI) and the depth of the epidural space during lumbar transforaminal ESIs.

Methods

Eighty-six consecutive patients undergoing lumbar transforaminal ESI at the L3-L4, L4-L5, and L5-S1 levels were studied. Using standard protocol, the foraminal epidural space was attained using fluoroscopic guidance. The measured distance from needle tip to skin was recorded (depth to foraminal epidural space). The differences in the needle depth and BMI were analyzed using regression analysis.

Results

Needle depth was positively associated with BMI (regression coefficient [RC], 1.13; P < 0.001). The median depths (in centimeters) to the epidural space were 6.3, 7.5, 8.4, 10.0, 10.4, and 12.2 for underweight, normal, preobese, obese I, obese II, and obese III classifications, respectively. Sex (RC, 1.3; P = 0.02) and race (RC, 0.8; P = 0.04) were also significantly associated with needle depth; however, neither factor remained significant when BMI was accounted as a covariate in the regression model. Age, intervertebral level treated, and oblique angle had no predictive value on foraminal depth (P > 0.2).

Conclusion

There is a positive association between BMI and transforaminal epidural depth, but not with age, sex, race, oblique angle, or intervertebral level.

Background and Objectives

Magnesium sulfate (MgSO4) is well-known as an antagonist of n-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO4 combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO4 could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic nerve block model. Further, the mechanism of possible synergy between LAs and MgSO4 was investigated in whole-cell mode patch-clamp experiments.

Methods

Sciatic nerves were exposed to 2%/73.9mM lidocaine, 0.25%/7.7mM bupivacaine, and 0.5%/15.4mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO4/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO4 interaction, voltage-dependent inactivation curves were determined in cultured rat GH3 cells expressing neuronal Na+ channels.

Results

Unexpectedly, the addition of MgSO4 overall significantly shortened the duration of blockade by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na+ channels in the presence of 300 μM lidocaine was almost unchanged by the addition of 10 mM MgSO4, indicating that MgSO4 does not affect the potency of lidocaine toward the inactivated Na+ channel.

Conclusions

MgSO4 coadministered with amide-type LAs shortened the duration of sciatic nerve blockade in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral nerve blockade. The mechanism of this observed antagonism is unclear, but appears to be independent of the action of LAs and MgSO4 at the LA receptor within the Na+ channel.