Malignant hyperthermia and dantrolene sodium / 대한마취과학회지

No abstract available.

Effects of adenosine receptor agonist on the rocuronium-induced neuromuscular block and sugammadex-induced recovery / 대한마취과학회지

BACKGROUND: Several types of receptors are found at neuromuscular presynaptic membranes. Presynaptic inhibitory A1 and facilitatory A2A receptors mediate different modulatory functions on acetylcholine release. This study investigated whether adenosine A1 receptor agonist contributes to the first twitch tension (T1) of train-of-four (TOF) stimulation depression and TOF fade during rocuronium-induced neuromuscular blockade, and sugammadex-induced recovery. METHODS: Phrenic nerve-diaphragm tissues were obtained from 30 adult Sprague-Dawley rats. Each tissue specimen was randomly allocated to either control group or 2-chloroadenosine (CADO, 10 μM) group. One hour of reaction time was allowed before initiating main experimental data collection. Loading and boost doses of rocuronium were sequentially administered until > 95% depression of the T1 was achieved. After confirming that there was no T1 twitch tension response, 15 min of resting time was allowed, after which sugammadex was administered. Recovery profiles (T1, TOF ratio [TOFR], and recovery index) were collected for 1 h and compared between groups. RESULTS: There were statistically significant differences on amount of rocuronium (actually used during experiment), TOFR changes during concentration-response of rocuronium (P = 0.04), and recovery profiles (P < 0.01) of CADO group comparing with the control group. However, at the initial phase of this experiment, dose-response of rocuronium in each group demonstrated no statistically significant differences (P = 0.12). CONCLUSIONS: The adenosine A1 receptor agonist (CADO) influenced the TOFR and the recovery profile. After activating adenosine receptor, sugammadex-induced recovery from rocuronium-induced neuromuscular block was delayed.

Unilateral postoperative visual loss in a patient undergoing hip arthroscopy in the supine position: a case report / 대한마취과학회지

Micro-emboli have been reported to occur commonly during arthroscopic surgery, which is frequently performed as an orthopedic surgical procedure. We here report a patient who experienced unilateral postoperative visual loss after a hip arthroscopy using irrigation fluid in the supine position without any evidence of external compression to either eye throughout the surgical procedure. Retinal fundoscopy suggested that the patient had central retinal artery occlusion, one of the causes of the postoperative visual loss. This case suggests that arthroscopic surgery may pose a substantial risk for paradoxical air embolism, such as central retinal artery occlusion, and suggests the need to prevent the entry of micro-air bubbles during such a type of surgery.

Comparison of warming methods for core temperature preservation during total knee arthroplasty using a pneumatic tourniquet

BACKGROUND: It is important to ensure that patients are normothermic during surgery. In total knee arthroplasty, the pneumatic tourniquet affects body temperature. We compared the ability of two warming devices to preserve core temperature in patients using a lower limb tourniquet under general anesthesia. METHODS: We included 132 patients with American Society of Anesthesiologists physical status I-II who were scheduled to undergo total knee arthroplasty. The patients were randomly divided into four groups (n = 33): group 1, without any heating method; group 2, with fluid warming; group 3, with forced-air warming; and group 4, with a combination of the two heating methods. After the induction of anesthesia, the esophageal and urinary bladder temperatures were monitored and recorded every 5 min before tourniquet deflation and every 1 min after tourniquet deflation. RESULTS: Before tourniquet deflation, compared with group 1, the odds ratios of groups 3 and 4 were less than 1. After tourniquet deflation, compared with group 1, the odds ratios of all groups using warming devices were less than 1. In particular, group 4 showed the largest hypothermia-preventive effect among the four groups. There was a significant correlation between esophageal temperature and bladder temperature before and after tourniquet deflation. CONCLUSIONS: After tourniquet deflation, a combination of a fluid warmer and forced-air warmer is the most effective method to prevent hypothermia, although either a fluid warmer or forced-air warmer alone could help to prevent hypothermia. Urinary bladder temperature changes correlate well with esophageal temperature changes throughout this operation.

Encountering unexpected difficult airway: relationship with the intubation difficulty scale / 대한마취과학회지

BACKGROUND: An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. METHODS: We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. RESULTS: For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. CONCLUSIONS: Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation.

Change in the effect of rocuronium after pneumatic tourniquet release in patients undergoing unilateral total knee arthroplasty

BACKGROUND: A pneumatic tourniquet is commonly used in orthopedic surgery. However, neuromuscular blocking agent can be sequestered in the isolated limb and be reabsorbed into the systemic circulation after tourniquet release, potentially delaying extubation. To investigate the change in the train-of-four (TOF) ratio after tourniquet release and correlate the TOF ratio change with the extubation time. METHODS: Forty patients undergoing unilateral total knee arthroplasty were enrolled. Before and after the pneumatic tourniquet release, 10 measurements of the TOF ratio were averaged and compared. Additionally, we investigated the correlation between the percentage change in the TOF ratio before and after tourniquet release and the extubation time. RESULTS: Among the 40 patient subjects, 30 showed a TOF ratio before tourniquet release and 10 showed only a TOF count. Of the 30 patients with a TOF ratio, 21 showed a TOF ratio increase after tourniquet release and 9 showed a TOF decrease; both increase and decrease were statistically significant (P < 0.001 and P = 0.008, respectively). The extubation time showed a weak negative correlation with the percentage change in the TOF ratio after tourniquet release (P = 0.004). CONCLUSIONS: In orthopedic surgery using a pneumatic tourniquet, neuromuscular function monitoring may be required to monitor the change in the effect of neuromuscular blocking agent before and after tourniquet release, which may help to improve anesthesia safety.

Perioperative cardiac arrest in 457,529 anesthetized patients at a single teaching hospital in Korea: a retrospective study

BACKGROUND: This study provides up-to-date survival data on cardiac resuscitation in adult in-patients. The main objectives of the study were to evaluate the incidence, causes, and outcomes of perioperative cardiac arrest. Objective data might encourage more meaningful attitude in anesthesiologists, surgeons, and patients. METHODS: We retrospectively reviewed patients who experienced perioperative cardiac arrest while receiving noncardiac surgery between January 2004 and December 2012. Collected data included patient characteristics, preoperative evaluations, American Society of Anesthesiologists Physical Status (ASA PS) classification, surgical status (e.g., elective or emergency), type of surgery, and outcomes. RESULTS: We identified 30 cases of perioperative cardiac arrest that occurred in 457,529 anesthetized patients (incidence = 0.66 per 10,000 anesthetized patient; all-cause mortality = 0.21 per 10,000 anesthetic cases). Two-thirds of patients (19 of 30) were emergency cases (21% survival rate; 4 of 19 patients). Most cardiac arrest patients (60%; 18 of 30 patients) were ASA PS IV-V, and only 40% patients were ASA PS I, II and III. Four cases were associated with anesthesia and the patient recovered, and 3 patients recovered after resuscitation. The main causes of cardiac arrest were respiratory- (75%) and medication-related events (25%). CONCLUSIONS: In accordance with anesthetic management guidelines and the development of anesthetic agents, anesthesia-related cardiac arrests decreased in terms of incidence and mortality. However, we recommend that clinicians cautiously keep in mind airway management and the administration of medications, which are important preventative factors.

General anesthesia versus sedation with dexmedetomidine for thoracic endovascular aortic repair in 38 patients in multicenter experiences: A retrospective study

BACKGROUND: Endovascular stent graft placement is a useful treatment option in lesions of the thoracic aorta. The aim of this study was to assess the possibility of sedation with dexmedetomidine compared with general anesthesia in patients undergoing thoracic endovascular aortic repair (TEVAR) in a multi-center clinical trial. METHODS: Data from 38 patients with thoracic aorta lesions treated by TEVAR between April 2010 and November 2013 were retrospectively collected at two hospitals. General anesthesia or sedation with dexmedetomidine was determined according to the hospital. Demographics, anesthetic recordings, and complications were reviewed. RESULTS: Stent graft placement was technically successful in all patients. There were no events during the anesthetic period. A total of 38 patients underwent TEVAR; 29 patients received general anesthesia, and 9 received sedation. Dexmedetomidine sedation (loading dose: 0.5-1.0 microg/kg for 10 min, maintenance: 0.2-0.8 microg/kg/h) was successfully performed without anesthesia-related complications or mortality. During the procedure, mean arterial pressure, heart rate, and saturation of peripheral oxygen were not statistically different between general anesthesia and dexmedetomidine sedation. CONCLUSIONS: In our study, TEVAR under sedation with dexmedetomidine was shown to be a feasible procedure that was well tolerated without specific complications.

Brugada syndrome manifested in postoperative period: A case report

We describe here a woman with Brugada syndrome revealed in postoperative period. A 48-year-old woman who underwent open biopsy of a tumor on her left distal femur under general anesthesia experienced post-surgical palpitations and chest discomfort. On the following day, an electrocardiogram showed coved type ST elevation with T inversion on V1 and V2 without any structural heart disease. After we confirmed it by a flecainide provocation test, the patient was diagnosed with Brugada syndrome. Genetic analysis showed c.3578G > A (p.Arg1193Gln) variant in the SCN5A gene. She underwent successful curettage and internal fixation under a single-shot spinal anesthesia without any adverse events.

Non-neurologic complications following surgery for scoliosis / 대한마취과학회지

BACKGROUND: The purpose of this study was to determine the prevalence of non-neurologic complications following surgery for scoliosis and to identify factors that can increase this risk. METHODS: The demographic data, medical and surgical histories, and prevalence of non-neurologic complications were reviewed in a retrospective cohort of 602 patients, who had undergone corrective surgery for scoliosis between January 2001 and June 2011. RESULTS: There were 450 patients under 20 years old (U20) and 152 of patients above 20 years old (A20) enrolled in this study. Forty-nine patients in U20 (10.9%) and 18 patients in A20 (11.8%) had post-operative complications. Respiratory complications were most common in U20 (4%) and gastrointestinal complications were most common in A20 (7%). There was no significant difference between the 2 groups in the prevalence of complications. Logistic regression revealed that factors that correlated with an increased odds for complications were Cobb angle (P = 0.001/P = 0.013, respectively), length of operation time (P = 0.003/P = 0.006, respectively), duration of anesthesia (P < 0.001/P = 0.005, respectively) and transfusion (P = 0.003/P = 0.015, respectively) in U20 and A20. Also, comorbidities (P = 0.021) in U20, and decreased body mass index (P = 0.030), pre-operative forced vital capacity (P = 0.001), forced expired volume in 1s (P = 0.001), increased numbers of vertebrae fused (P = 0.004), blood loss (P = 0.001) in A20 were associated with increased odds for complications. CONCLUSIONS: There was no difference in the prevalence of complication in scoliosis patients by age. The prevalence of complication was dependent on Cobb angle, length of operation time, duration of anesthesia and transfusion of PRBC. Deterioration of preoperative pulmonary function significantly increased risk of post-operative complications in adult patients.

Axillary approach versus the infraclavicular approach in ultrasound-guided brachial plexus block: comparison of anesthetic time / 대한마취과학회지

BACKGROUND: With ultrasound guidance, the success rate of brachial plexus block (BPB) is 95-100% and the anesthetic time has become a more important factor than before. Many investigators have compared ultrasound guidance with the nerve stimulation technique, but there are few studies comparing different approaches via the same ultrasound guidance. We compared the axillary BPB with the infraclavicular BPB under ultrasound guidance. METHODS: Twenty-two ASA physical status I-II patients presenting with elective forearm surgery were prospectively randomized to receive an axillary BPB (group AX) or an infraclavicular BPB (group IC) with ultrasound guidance. Both groups received a total of 20 ml of 1.5% lidocaine with 5 microg/ml epinephrine and 0.1 mEq/ml sodium bicarbonate. Patients were then evaluated for block onset and block performance time was also recorded. RESULTS: Group IC demonstrated a reduction in performance time vs. group AX (622 +/- 139 sec vs. 789 +/- 131 sec, P < 0.05). But, the onset time was longer in group IC than in group AX (7.7 +/- 8.8 min vs. 1.4 +/- 2.3 min, P < 0.05). All blocks were successful in both groups. CONCLUSIONS: Under ultrasound guidance, infraclavicular BPB was faster to perform than the axillary approach. But the block onset was slower with the infraclavicular approach.

Survey of malignant hyperthermia in Korea: Report for the necessity of establishing the center for caffeine and halothane contracture test in Korea: a questionnaire

BACKGROUND: Malignant hyperthermia (MH) has a high mortality rate and a family history. Then, caffeine and halothane contracture test (CHCT), generally used to detect MH susceptibility, is needed for early detection. The aim of this survey is to collect the opinion about establishment of the center for CHCT in Korea. METHODS: A people who were anesthesiologists working in the training hospital of Korea participated the survey between January and March 2011. Usual anesthetic drug during general anesthesia including volatile agents, opioids, muscle relaxants, incidence, diagnoses and treatments of MH, and opinion about establishment of the center for CHCT, were investigated. RESULTS: A total of 105 people who were anesthesiologists working in Korea were registered, they answered that 33 anesthesiologists (32%) met MH patient, and MH occurred once in a decade. If there is a diagnostic method such as CHCT in Korea, 89 anesthesiologists (89%) will recommend the test for the patients and their family. CONCLUSIONS: Many anesthesiologists want to recommend the CHCT for patients and their family. But, in Korea, it is impossible because there is no laboratory available for CHCT. Now, we considered carefully to establish the laboratory available for CHCT.

Controlling deliberate hypotension in hypertensive patients undergoing spinal surgery: a comparison between remifentanil and sodium nitroprusside

BACKGROUND:This study was designed to determine whether remifentanil or sodium nitroprusside (SNP) with sevoflurane anesthesia can induce safe deliberate hypotension (DH) to a target mean arterial pressure (MAP) of 55-65 mmHg in patients with controlled hypertension. METHODS:Thirty patients with controlled hypertension and who were scheduled for posterior lumbar interbody fusion were randomly assigned to receive remifentanil (n = 15, group R) or SNP (n = 15, group S).All the patients received a balanced anesthetic technique including 1.5-2 vol% sevoflurane.Group R received remifentanil by target-controlled infusion.The infusion was initiated with a target concentration at 4 ng/ml and this was adjusted every 1 min by 1 ng/ml to maintain the MAP to the target level of 55-65 mmHg.In group S, the infusion of SNP was initiated at 1 ug/kg/min and this was increased by 0.5 ug/kg/min.Cerebral oximetry was done and the cardiac index was measured with esophageal Doppler. RESULTS:DH was achieved at a MAP = 60 mmHg within 5.7 min for group R and 3.7 min for group S.The intraoperative blood loss was lower in Group R than that in Group S (304 +/- 103 vs 650 +/- 141 ml, P < 0.05).The frequency of added ephedrine injection to control the MAP and discontinuation of the study drug due to a MAP < 60 mmHg were higher in group S than in group R (46% vs 13%, P < 0.05 and 62% vs 20%, P < 0.05, respectively). CONCLUSIONS:Compared to SNP, remifentanil with sevoflurane anesthesia induced safer DH for patients with controlled hypertension.

Comparison of airwayscope to direct laryngoscope and lightwand for cardiovascular response in patients with difficult airway / 대한마취과학회지

BACKGROUND: Airwayscope (AWS), which has been used successfully for difficult airway in general anesthesia, has been anticipated that hemodynamic response to tracheal intubation in the difficult airway may be attenuated. Also, there is a series of reports demonstrating the successful use of lightwand to open the difficult airway. Thus, we decided to conduct a survey to compare AWS to lightwand and to direct laryngoscopy of cardiovascular response to tracheal intubation. METHODS: Of 64 healthy patients without cardiovascular disease, 22, 21, 21 patients were randomly assigned to AWS group, lightwand group and direct laryngoscope group. After induction of general anesthesia, intubation was performed with manual in-line neck stabilization. During laryngoscopy, a modified Cormack-Lehane grade was assessed and time to intubation was measured. Systolic arterial pressure (SAP) and heart rate (HR) were recorded at the following timepoints: baseline, just before intubation, 1 min, 2 min, 3 min, 4 min and 5 min after intubation. RESULTS: There were no significant differences between the 3 groups in SAP, HR (P > 0.05). However modified Cormack-Lehane grade of all patients in the AWS group was I, while that in direct laryngoscope group was IIB or III. In addition, the mean time to intubation of the direct laryngoscope group was significantly longer than that of the AWS and lightwand (P < 0.05). CONCLUSIONS: In the difficult airway, AWS was very effective in improving laryngeal view and decreasing time to intubation compared to direct laryngoscopey. In addition, lightwand reduced the time to intubation. However we could not find any significant difference in hemodynamic response to tracheal intubation among the 3 groups.

Manipulation of frozen shoulder under monitored anesthesia care with propofol and remifentanil / 대한마취과학회지

BACKGROUND: Manual manipulation under anesthesia in primary frozen shoulder is recommended for restoring range of motion and improving function. Usually, manipulation is performed briefly under general anesthesia, which accompanies some anesthesia- related risks for outpatients. METHODS: 12 patients suffered from primary frozen shoulder were received manipulation under monitored anesthesia care (MAC) with propofol (1 mg/kg) and remifentanil (25microgram) as an initial dose. And then we injected additional bolus dose (propofol 20 mg, remifentanil 10microgram) in case of inadequate sedation. After manipulation, sodium hyaluronate 20 mg, 0.75% ropivacaine 22.5 mg and ketorolac 30 mg were injected into the glenohumeral joint. Clinical data were gathered at baseline and at 4 weeks after manipulation. RESULTS: The procedure was carried out successfully under MAC. Clinical results including improvements of visual analogue scale of pain and range of motion were comparable to previous studies. 2 patients who received relatively large doses of anesthetics have required triple airway maneuver and manual mask ventilation for 1 to 2 minutes respectively because of desaturation below 90%. There are not any serious adverse effects. CONCLUSIONS: MAC with propofol and remifentanil makes it possible to get adequate level of sedation for shoulder manipulation and to reduce recovery time from anesthesia at the same time. MAC, therefore, is the adequate outpatient anesthetic method for shoulder manipulation.

Severe Neck Edema after Shoulder Arthroscopy : A case report

Although shoulder arthroscopy has provided a major advantage in the diagnosis and treatment of shoulder injuries, it is not free of complications. Several clinical reports have described patients who suffered life-threatening airway obstruction during arthroscopic shoulder surgery performed under regional or general anesthesia. We report a case of severe neck edema threatening airway after shoulder arthroscopy under general anesthesia.

Sniffing Position Improves the Laryngeal View Regardless of Body Mass Index / 대한마취과학회지

BACKGROUND: Most anesthesiologists universally recommend the sniffing position and consider it to be essential for improving the performance of orotracheal intubation. However, a recent investigation reported that the sniffing position does not aid the laryngoscope except under specific circumstances (i.e., obesity). Therefore, this study examined the impact of the BMI (body mass index) on the effectiveness of the sniffing position in improving the laryngeal view. METHODS: A video laryngoscopy imaging system and POGO (the percentage of glottic opening) scoring system were used to assess the laryngeal view in 79 adult patients undergoing a laryngoscopy. In each patient, the laryngeal view was videotaped continuously from simple head extension to the sniffing position by inflating a pressure bag as a pillow to obtain approximately 15o of flexion of the lower cervical spine on the chest. The variables assessed included the BMI, the POGO score in each position and the change in the POGO score. RESULTS: The POGO scores improved with the sniffing position (18.1 +/- 14.3%). However, the sniffing position did not improve the POGO score in 16/79 (20.3%) patients. The sniffing position did not worsen the POGO score in any patient. No significant correlation was found between the BMI and the change in the POGO score in the sniffing position (Pearson's correlation coefficient r = 0.075). CONCLUSIONS: The sniffing position has the potential to improve the laryngeal view in all intubations without needing to consider the BMI. Therefore, the sniffing position appears to be advantageous for orotracheal intubation compared with a simple head extension.

Influence of Myoendothelial Gap Junction on the Regulation of Vasomotor Tone / 대한마취과학회지

BACKGROUND: In addition to nitric oxide (NO) and prostacyclin (PGI2), there is another endothelium-derived mechanism of smooth muscle relaxation, which is associated with an endothelium-derived hyperpolarizing factor (EDHF). To assess the role of gap junctions in endothelium dependent hyperpolarization, we investigated the relationship between distribution of myoendothelial gap junction (MEGJ) and relative importance of the EDHF pathway in the regulation of vascular tone. METHODS: Immunohistochemistry and confocal microscopic examination of the mesenteric arterial wall of male Sprague-Dawley rat following treatment with specific antibodies were performed to delineate the distribution of connexin 43, a gap junctional protein. The standard dose-response curve for acetylcholine (10-9-10-5 M) of the mesenteric artery was regarded as the release of EDHF in the presence of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 10-4 M) and indomethacine (10-5 M). The effects of the gap junction inhibitors such as 18alpha-glycyrrhetinic acid (18alpha-GA; (2 x 10-4 M)) and carbenoxolone (3 x 10-4 M) was assessed regarding relaxtion to acetylcholine, contraction to phenylephrine (5 x 10-6 M) in the proximal and distal mesenteric arteries. RESULTS: In the distal artery, gap junctional plaques were more prevalent, and the relaxation response to acetylcholine was augmented and the contraction response to phenylephrine was depressed compared with the proximal artery. In both the proximal and distal mesenteric arteries, acetylcholine-induced relaxations attributable to EDHF were near completely blocked by 18alpha-GA and carbenoxolone to the same degree. Regardless of the presence of L-NAME plus indomethacin, 18alpha-GA significantly augmented the contraction response to phenylephrine. CONCLUSIONS: The vasomotor regulatory response by EDHF in the rat mesenteric arteries may be explained by extensive heterocellular coupling through MEGJs. Moreover, the release of EDHF through MEGJ may have a essential role in the regulation of resistor arterial tone.

Survey of Central Venous Catheter Depth Using the Carina as a Radiologic Landmark in ICU Patients / 대한마취과학회지

BACKGROUND: There is no unique guideline as to how to determine the depth of a central venous catheter (CVC). In this study, we inspected the current practice of CVC placement and evaluated insertion depth using the carina as a radiologic landmark in intensive care unit (ICU) patients. METHODS: In 138 ICU patients with a CVC in the right subclavian (SCV group) or internal jugular vein (IJV group), a chest X ray was taken, and the radiographic vertical distance between the catheter tip and the carina level (D-CC) was measured in Picture Archiving and Communication System (PACS) view. The distance between the skin puncture site and the carina level (D-SC) was calculated by adding/subtracting D-CC to/from the actual CVC insertion length. In addition, we surveyed physicians using a questionnaire about the methods they used to determine CVC depth. RESULTS: Mean D-SC was 13.80 +/- 1.69 cm in the SCV group, 14.42 +/- 1.34 cm in the IJV group, but no correlation was found with any measured physical dimension. In males, D-SC was greater, but this difference was not statistically significant. Physicians determined required insertion depths using many different methods (e.g., height, sex......). CONCLUSIONS: Patient height, weight, body mass index (BMI), and sex were not found to be reliable for predicting a safe CVC length. We recommend that after CVC insertion, a chest X ray should be taken and the catheter tip repositioned if necessary to reduce catheter related fatal complications (e.g., cardiac tamponade).

The Role of Nitric Oxide Synthase Isoforms in Neuropathic Pain Induced by Nerve Injury in Rats / 대한마취과학회지

BACKGROUND: Peripheral nerve injury may generate pain hypersensitivity, characterized by enhanced nociceptive responses to noxious stimuli and decreased thresholds to innocuous stimuli, and may lead to a chronic neuropathic pain state resulting from an increase in central neuron excitability. This central sensitization is mediated via N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). In this work, we investigated whether the action of NO and local nitric oxide synthase (NOS) expression play a role in neuropathic pain in a rat model. METHODS: Neuropathic pain was produced by resecting two branches of the sciatic nerve. N-nitro-L-arginine methyl ester (L-NAME) (a nonselective NOS inhibitor), or 7-nitroindazole (7-NI) (a neuronal NOS (nNOS) inhibitor), or aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) were administered locally for 2, 7, or 14 days via osmotic pumps. Behavioral tests for pain were conducted after nerve injury using mechanical and thermal stimuli applied to the hind paws. We used immunohistochemical methods to provide evidence for endothelial NOS (eNOS), nNOS, and iNOS expression. RESULTS: Following nerve injury, significant mechanical allodynia and thermal hyperalgesia were observed in rats treated with AG or 7-NI. In contrast, when L-NAME, a known potent inhibitor of eNOS was applied locally, no significant mechanical allodynia or thermal hyperalgesia was observed. No dependency on the route or duration of NOS inhibitor administration was noted. Increased immunoreactivities of the eNOS and nNOS isoforms were intense and discrete at 48 hour following nerve injury, unlike sham exposed intact nerves. In 14 day stumps, iNOS staining was observed in the endoneurium and perineurium. eNOS immunoreactivity at 2 days after nerve injury was not observed in L-NAME treated rats. At 14 days after nerve injury, iNOS immunoreactivity was rarely observed in AG and L-NAME treated rats. CONCLUSIONS: Our results indicate that an early eNOS expression plays a critical role in the development of neuropathic pain.