Lipid Emulsion in the Successful Resuscitation of Local Anesthetic Toxicity after Ankle Block / 대한구급학회지

Unexpected occurrence of local anesthetic toxicity is not rare and can cause fatal complications that do not respond to any known drug of intervention. Recently, the successful use of lipid emulsion for local anesthetic toxicity has been reported and recommended as a rescue method for cardiac or neurologic complications. We report a case of seizure attack and respiratory arrest successfully recovered with the use of intravenous lipid emulsion. Clinicians must be aware of the beneficial role of lipid emulsion in cases of local anesthetic toxicity.

Anesthetic requirements and stress hormone responses in chronic spinal cord-injured patients undergoing surgery below the level of injury: nitrous oxide vs remifentanil / 대한마취과학회지

BACKGROUND: Nitrous oxide (N2O) and remifentanil both have anesthetic-reducing and antinociceptive effects. We aimed to determine the anesthetic requirements and stress hormone responses in spinal cord-injured (SCI) patients undergoing surgery under sevoflurane anesthesia with or without pharmacodynamically equivalent doses of N2O or remifentanil. METHODS: Forty-five chronic, complete SCI patients undergoing surgery below the level of injury were randomly allocated to receive sevoflurane alone (control, n = 15), or in combination with 67% N2O (n = 15) or target-controlled infusion of 1.37 ng/ml remifentanil (n = 15). Sevoflurane concentrations were titrated to maintain a Bispectral Index (BIS) value between 40 and 50. Measurements included end-tidal sevoflurane concentrations, mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine and cortisol concentrations. RESULTS: During surgery, MAP, HR, and BIS did not differ among the groups. Sevoflurane concentrations were lower in the N2O group (0.94 +/- 0.30%) and the remifentanil group (1.06 +/- 0.29%) than in the control group (1.55 +/- 0.34%) (P < 0.001, both). Plasma concentrations of norepinephrine remained unchanged compared to baseline values in each group, with no significant differences among groups throughout the study. Cortisol levels decreased during surgery as compared to baseline values, and returned to levels higher than baseline at 1 h after surgery (P < 0.05) without inter-group differences. CONCLUSIONS: Remifentanil (1.37 ng/ml) and N2O (67%) reduced the sevoflurane requirements similarly by 31-39%, with no significant differences in hemodynamic and neuroendocrine responses. Either remifentanil or N2O can be used as an anesthetic adjuvant during sevoflurane anesthesia in SCI patients undergoing surgery below the level of injury.

Protective Effect of Sauchinone Against Regional Myocardial Ischemia/Reperfusion Injury: Inhibition of p38 MAPK and JNK Death Signaling Pathways

Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3beta was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% +/- 5.3% in the sauchinone group vs 44.4% +/- 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3beta was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.

Fatal pulmonary embolism caused by thrombosis of contralateral axillary vein after arthroscopic right rotator cuff repair: A case report / 대한마취과학회지

A clinically apparent thromboembolism associated with arthroscopic shoulder surgery is extremely rare. We report a case of a fatal pulmonary embolism developed after an arthroscopic rotator cuff repair in a 45-year-old woman. On the first day after surgery, she experienced syncope that was complicated by cardiac arrest. No hemostasis impairment was noted. A computed tomography scan revealed a pulmonary embolism, and Doppler ultrasound revealed thrombosis of the axillary vein on the contralateral shoulder. She died from multiple organ failure 13 days after surgery. This case shows that clinicians must be aware of the potential occurrence of a pulmonary thromboembolism in patients undergoing prolonged arthroscopic shoulder surgery.

Reexpansion Pulmonary Edema Following the Early Decompression of Pneumothorax Occurred after Anesthetic Induction in a Patient with Lung Bulla: A Case Report / 대한구급학회지

When a rapidly re-expanding lung has been in a state of collapse for more than several days, pulmonary edema sometimes occurs. This is called reexpansion pulmonary edema. In general, it most commonly occurs in patients with a large pneumothorax of long duration. In this case, a 15 year old female patient with a 2.3 cm sized bulla in the right lung developed right pneumothorax after anesthetic induction. Although early drainage by closed thoracostomy was performed, right pulmonary edema eventually occurred. It is unusual that vigorous reexpansion pulmonary edema developed even though early decompression was performed within one hour after development of pneumothorax.

Effect of ulinastatin on cytokine reaction during gastrectomy / 대한마취과학회지

BACKGROUND: Inflammation plays an important role in the postoperative morbidity of organs, which is related to the activation of pro-inflammatory and anti-inflammatory cytokines. Ulinastatin (Urinary trypsin inhibitor, UTI) is a serine protease inhibitor found in human urine or serum that inhibits the activation of human leukocyte elastase. This study examined the effect of UTI on the inflammation response in patients undergoing a gastrectomy. METHODS: Thirty patients scheduled to undergo a gastrectomy were divided into two groups as follows: Control group (untreated, n = 15) and UTI group (100,000 units of UTI were continuously injected intravenously for 2 hours, n = 15). Arterial blood was sampled before surgery (T0), 10 minutes after its onset (T1), at its end (T2), and 1 hour after surgery (T3) to measure the level of cytokines. RESULTS: Both the control and treatment groups had higher interleukin (IL)-6 levels at T2 and T3 than T0, and the level increased with time. However, the increase was smaller in the treatment group. The IL-8 levels were not activated significantly in any of the groups. CONCLUSIONS: UTI inhibits the secretion of IL-6, which is an inflammatory cytokine produced after a gastrectomy. This shows that UTI can decrease the inflammation reaction caused by surgical stress.

Tracheal laceration found after endotracheal general anesthesia : A case report

Tracheal laceration is a rare complication after endotracheal intubation with an estimated incidence of 1:10,000. We present a case of tracheal laceration after general anesthesia with endotracheal intubation. A 63-year-old woman underwent ureteroscopic stone removal under the general anesthesia. She had history of treatment for hypertension and DM for 10 years. Surgery, anesthesia and recovery phase were uneventful. Postoperative first day, patient complained chest discomfort and chest radiography showed the clinical diagnosis of marked subcutaneous emphysema and pneumomediastinum. Postoperative second day, chest CT scan revealed laceration of the posterior tracheal wall extending from the middle of the trachea to the level of 5 cm above carina. Surgical repair was done. We review risk factors, diagnosis and principles of treatment of this lesion.

Effect of mixed administration of propofol and rocuronium on intubating conditions / 대한마취과학회지

BACKGROUND: We investigated whether the intubating condition change acoording to the methods of administration of propofol and rocuronium. METHODS: Ninety adult patients (ASA physical status I or II) undergoing elective surgery were randomly assigned to one of three groups; Group I (n = 30) received rocuronium (0.6 mg/kg) after administration of propofol (2 mg/kg), Group II (n = 30) received propofol and rocuronium simultaneously via different intravenous routes, and Group III (n = 30) received a mixture of propofol and rocuronium via same intravenous route. Intubation was attempted at 60 seconds after administration of rocuronium. Hemodynamic parameters (mean blood pressure, heart rate) were measured before and after propofol administration with 20 seconds interval. Intubating conditions (jaw relaxation, vocal cord movement, and response to tracheal intubation) were evaluated as excellent, good, fair and poor. Train of four counts were recorded at 60 seconds after administration of rocuronium. RESULTS: Excellent intubating conditions were obtained in 13% in group I, 60% in group II, 77% in group III. Mean train of four counts were 3.7 in group I, 3.4 in group II, and 3.5 in group III. Mean blood pressures were decreased gradually after propofol administration in all groups. However, heart rates were not changed in all groups. CONCLUSIONS: At induction of anesthesia, simultaneous or mixed administration of propofol and rocuronium provides excellent or good intubating conditions 60 seconds after rocuronium administration. It could be an effective alternative to succinylcholine for rapid sequence induction of anesthesia.

Comparison of intubating conditions and hemodynamic responses to tracheal intubation with different effect-site concentrations of remifentanil without muscle relaxants during target-controlled infusion of propofol / 대한마취과학회지

BACKGROUND: We compared the effects of different remifentanil effect-site concentrations on intubating conditions, and cardiovascular and bispectral index score (BIS) responses to intubation at a fixed effect-site concentration of propofol without muscle relaxants. METHODS: Sixty-four patients were randomly assigned to one of three groups: remifentanil 2 (group R2, n = 22), 4 (group R4, n = 21), or 6 ng/ml (group R6, n = 21). Anesthesia was induced using target-controlled infusion of propofol 5 microgram/ml and each concentration of remifentanil. Laryngoscopy and intubation was attempted at 2.5 min following induction. Intubating conditions were assessed as excellent, good or poor using a standard scoring system. Mean arterial pressure (MAP), heart rate (HR), and BIS values were assessed. RESULTS: Excellent or good intubating conditions were obtained in 91% of group R4 and 95% of R6, both of which are higher compared with 32% of R2 (P < 0.01). MAP and HR decreased significantly after induction in all groups. After intubation, they recovered to baseline value in group R2 and R4 but were significantly less than baseline values in R6. BIS response to intubation was attenuated in group R4 and R6 but not R2. Hypotension was more frequent in group R6 than R2. CONCLUSIONS: Remifentanil target concentrations of 4 or 6 ng/ml combined with 5 microgram/ml propofol provided good or excellent conditions for tracheal intubation and prevented cardiovascular and BIS response during induction without muscle relaxants. However, the use of 6 ng/ml dose was associated with frequent occurrence of hypotension and bradycardia requiring treatment.

Hemodynamic and Catecholamine Responses to Laryngoscopy and Endotracheal Intubation in Paraplegic Patients: Time Course and Relation to the Affected Level / 대한마취과학회지

BACKGROUND: We determined whether the cardiovascular responses to endotracheal intubation change as a function of the time elapsed after injury and the level of injury in patients with spinal cord injury. METHODS: One-hundred-eighty six patients with complete cord injury were grouped into 3 according to the level of injury:high- (T1-T4, n = 34), mid- (T5-T10, n = 47) and low paraplegics ( 10 yrs.Twenty-five patients with no cord injury served as controls.Systolic arterial blood pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were measured. RESULTS: The intubation caused an increase of SAP and norepinephrine concentrations in every group.However, the magnitude of their peak increases was less in high paraplegics compared with all other groups (P < 0.05).HR was similarly increased in all groups (P < 0.01).Pressure but not either HR or norepinephrine response was enhanced in mid- and low-paraplegics whose injury elapsed more than 10 yrs compared with controls (P < 0.05).The incidence of arrhythmias did not differ among the groups. CONCLUSIONS: The pressure and plasma catecholamine changes associated with endotracheal intubation may be attenuated in high-paraplegics, and the pressure changes may be enhanced over time in mid- and low-paraplegics.

Anesthetic Requirements in Chronic Cord-injured Patients Undergoing Surgery below the Level of Injury / 대한마취과학회지

BACKGROUND: We determined the effect of spinal cord injury (SCI) on sevoflurane requirements and stress hormone responses, and sevoflurane concentration to block autonomic hyperreflexia (AHR) in SCI patients. METHODS: In the first series, sevoflurane concentrations to maintain bispectral index score (BIS) at 40-50 and stress hormone response were examined in 27 SCI patients undergoing surgery below the level of injury.Fifteen patients without SCI served as control.Measurements included end-tidal sevoflurane concentrations (ET(SEVO)), systolic blood pressure (SBP), heart rate (HR), catecholamines, vasopressin, and cortisol concentrations.In the second series, sevoflurane concentration to block AHR was examined in 31 SCI patients undergoing transurethral litholapaxy.When a patient developed an episode of AHR, the target sevoflurane concentration was maintained for 10 min, and then the procedure was repeated.Each target concentration was determined by up-down method based on SBP. RESULTS: During surgery, SBP, HR, and BIS were comparable between SCI and control.However, ETSEVO was significantly smaller in the SCI than the control.Plasma concentrations of norepinephrine, epinephrine and cortisol were significantly lower in the SCI than the control.SBP rose by 67 +/- 31 mmHg, whereas HR fell by 13 +/- 8 bpm during the 1st trial in the SCI (P < 0.01).Hypertensive events were associated with increases of norepinephrine concentrations.ETSEVO required to prevent AHR were 3.12% in 50% of patients, 3.83% in 95% of patients. CONCLUSIONS: SCI reduces the anesthetic requirement by 39%, and decreases stress hormone responses during surgery below the level of injury.To prevent AHR in 95% of SCI patients undergoing litholapaxy, ETSEVO 3.83% may be required.

Anesthetic Management for a Patient with Congenital Insensitivity to Pain with Anhidrosis (CIPA): A case report / 대한마취과학회지

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, autosomal-recessive disorder characterized by the clinical triad of indifference of pain, anhidrosis and heat intolerance.Because of their lack of autonomic response to noxious stimuli, the determination of adequate depth of anesthesia in the CIPA patient undergoing surgery is a major challenge.We experienced a patient with CIPA who had minor procedures three times under the general anesthesia, in which bispectral index (BIS) was maintained at 40-50 by adjusting sevoflurane concentrations with 50% nitrous oxide.The low end-tidal sevoflurane concentrations (<1.2 vol%) were required to keep the target BIS while vital signs remained stable throughout the surgery in each operation.BIS monitor may be a valuable tool to guide the depth of anesthesia in patients with CIPA.

Effects of Nitrous Oxide and Remifentanil on Cardiovascular Response to Endotracheal Intubation during Desflurane Anesthesia

BACKGROUND: Desflurane is known to causes hypertension and tachycardia when its inspired concentration is rapidly increased. We determined whether nitrous oxide (N2O) or remifentanil alters cardiovascular responses to intubation and/or inhalation of high concentrations of desflurane during induction of anesthesia. METHODS: Sixty patients were assigned randomly into three groups (n = 20 each). Anesthesia was induced with thiopental 5 mg/kg followed by saline (control and N2O groups) or remifentanil 1microg/kg (remifentanil group). Tracheal intubation was facilitated with intravenous vecuronium 0.12 mg/kg and 12% desflurane was given soon after the intubation. In addition, 75% N2O was given beginning 3 min before the intubation in the N2O group. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were determined. RESULTS: The intubation resulted in an immediate increase and an additional second increase of SAP and HR at 3 to 5 min after intubation in all groups. SAP but not HR in the N2O group and both SAP and HR in the remifentanil group at first and second peak responses were lower than in the control group. Norepinephrine increased at 1 min after intubation and increased further at 5 min in the control and N2O groups but only increased at 5 min in the remifentanil group. CONCLUSIONS: A biphasic pressor and tachycardiac response in response to intubation and desflurane were noted. Although N2O did not affect tachycardiac response, it suppressed the pressor responses and augmented norepinephrine release. However, remifentanil significantly attenuated hemodynamic and catecholamine responses to endotracheal intubation and desflurane.

Hemolytic Uremic Syndrome Occurred after Esophagectomy: A Case Report / 대한구급학회지

Hemolytic uremic syndrome is an unusual and uncommon disease in adults but more common in children, which is defined by the triad of acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. We report a 64-year-old man who developed hemolytic uremic syndrome after esophagectomy and esophagogastrostomy due to esophageal cancer. We treated him using continuous renal replacement therapy and plasmapheresis with large volume fresh frozen plasma transfusion for 9 days. We could not find the cause of hemolytic uremic syndrome, and so finally concluded that it is idiopathic. Bleeding continuously without a particular reason after an operation, it needs an early diagnosis and treatment with considering a possibility of the hemolytic uremic syndrome.

Effects of Remifentanil and Alfentanil on Cardiovascular Responses to Laryngoscopy and Double-lumen Endobronchial Intubation / 대한마취과학회지

BACKGROUND: This study examined the cardiovascular responses to double-lumen endobronchial intubation during rapid sequence induction of anesthesia, and compared the effect of remifentanil and alfentanil in a randomized, double-blind, placebo-controlled study in three groups of 20 elderly patients each. METHODS: Anesthesia was induced with intravenous thiopental (4-6 mg/kg) immediately followed by either remifentanil 2 microgram/kg, alfentanil 30microgram/kg, or saline (placebo) given over 30 sec. Succinylcholine 1.5 mg/kg was given for neuromuscular block. The laryngoscopy and intubation were performed 60 sec later. RESULTS: The intubation significantly increased systolic arterial pressure (SAP) and heart rate (HR) in all groups. The maximum pressure changes in the remifentanil and alfentanil groups (36 +/- 26 and 33 +/- 30 mmHg, respectively) were significantly lower than the 83 +/- 35 mmHg in the control group. The maximum HR in the remifentanil (77 +/- 13 bpm) and alfentanil (80 +/- 13 bpm) groups was lower when compared to controls (93 +/- 11 bpm). The norepinephrine and epinephrine concentrations increased after intubation in the control group but remained unaltered in both the alfentanil and remifentanil groups. There were no significant differences between the remifentanil and alfentanil groups in HR, SAP or catecholamines at any time. Five patients in the remifentanil group and three in the alfentanil group received ephedrine for hypotension. CONCLUSIONS: Endobronchial intubation elicited a significant pressor response, and that both remifentanil and alfentanil similarly attenuated the pressor response. However, the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.

Analgesic Effect of Epidural Fentanyl-Neostigmine after Radical Subtotal Gastrectomy / 대한마취과학회지

BACKGROUND: This study evaluated the efficacy of an epidural single dose of neostigmine combined with fentanyl to provide postoperative analgesia after radical subtotal gastrectomy. METHODS: Fifty two adults patients with ASA physical status 1 and 2 are randomly allocated to receive a single injection of either epidural fentanyl 100 microgramor combination of fentanyl 100microgram with neostigmine 250, 500 and 750microgramin a total volume of 10 ml. Pain scores were recorded after 0, 5, 10, 15, 20, 30 mins to determine the onset of analgesia. Patients' vital signs as well as side effects were monitored at regular intervals. RESULTS: Patients' demographic data were not different from each other. Epidural neostigmine 750 microgram with fentanyl 100 microgram produced effective analgesia (visual analog scale at 10 min ; 35 +/- 10.6 mm). The time to first rescue analgesics administration was significantly longer in the neostigmine group (250 microgram: 84.2 +/- 9.4, 500 microgram: 90.9 +/- 7.1, 750 microgram: 92.5 +/- 14.4 min) than the control group (53.0 +/- 20.0 min). CONCLUSIONS: Combination of fentanyl with neostigmine was proven to be more effective for treating postoperative pain after subtotal gastrectomy than fentanyl alone. Additionally, the most effective dose of epidural neostigmine was 750microgram.

The Effect of Doxapram Hydrochloride on the Ventilation Responses during Total Intravenous Anesthesia by Laryngeal Mask Airway / 대한마취과학회지

BACKGROUND: Intravenous anesthetics causes depression of ventilatory response to hypercapnea. Doxapram stimulates ventilation via peripheral and central chemoreceptors. This study was aimed to evaluate the effect of doxapram on ventilation during total intravenous anesthesia (TIVA). METHODS: 60 patients undergoing operation under spontaneous ventilation via laryngeal mask airwaywere randomly divided into 3 groups: Control group received 5% dextrous infusion, D-2 group received doxapram injection of 1 mg/kg followed by continuous infusion of 2 mg/kg/hr, and D-4 group received doxapram injection of 2 mg/kg followed by continuous infusion of 4 mg/kg/hr. Anesthesia was induced and maintained with propofol and remifentanil. Respiratory rate, tidal volume (VT) and arterial carbon dioxide tension (PaCO2) were measured before and 15 min after induction of anesthesia, 0(15 min after start of operation), 1, 2, 3, 5, 15, 30, 45, and 60 min after start of doxapram infusion during TIVA. RESULTS: VT was significantly increased 1 min after start of doxapram infusion and returned to the value of pre-doxapram infusion immediately. In D-4 group, VT was significantly (P < 0.05) increased again 5 min after doxapram infusion compared with the value of pre-doxapram infusion and control group. PaCO2 was decreased 1 min after start of doxapram infusion and then increased again 2 min after doxapram infusion. In D-4 group, the degree of increase of PaCO2 was significantly (P < 0.05) less than those of D-2 group. CONCLUSIONS: Doxapram injection of 2 mg/kg followed by continuous infusion of 4 mg/kg/hr improved the depression of ventilatory response during TIVA.

Bispectral Index Values at a Sevoflurane Concentration of 1% in Patients Undergoing Lower Segment Cesarean Delivery: A Comparison between Painful Labor and Painless Labor / 대한마취과학회지

BACKGOUND: An end-tidal concentration of 1% sevoflurane with 50% nitrous oxide (N2O) during a Cesarean section resulted in bispectral index (BIS) values > 60, which are considered at risk for awareness. The present study aimed to determine whether the presence or absence of labor pain prior to the Cesarean section would affect the BIS value. METHODS: Sixty women scheduled to undergo Cesarean section under general anesthesia, were allocated to three groups of 20 patients: women undergoing elective surgery without labor pain (group 1, control), or emergency surgery without (group 2) or with (group 3) active labor pain. After endotracheal intubation, anesthesia was maintained with end-tidal 1% sevoflurane and 50% N2O in oxygen throughout the surgery. The BIS value, systolic blood pressure and heart rate were measured before (baseline) and during the induction of anesthesia, intubation, skin incision, uterine incision, delivery and at 1, 3, 5 and 10 min after delivery. Neonatal effects were assessed using Apgar scores at 1 and 5 min after delivery. RESULTS: BIS values were significantly lower in group 3 than in groups 1 and 2 throughout the study, except at baseline and induction (P < 0.05). However, the systolic blood pressure, heart rate and Apgar scores did not differ among the three groups. CONCLUSIONS: These results demonstrate that 1.0% sevoflurane combined with 50% N2O results in BIS values < 60 during Cesarean delivery in women with active labor pain but not in those without active labor pain, consistent with an adequate depth of anesthesia to prevent recall.

Potentiation of Morphine's Antinociception by Group II and Group III Metabotropic Glutamate Receptors Agonists on a Rat Incisional Pain / 대한통증학회지

BACKGROUND: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. METHODS: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. RESULTS: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. CONCLUSIONS: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

Antinociceptive Effects of Intrathecal Melatonin on Formalin: and Thermal-induced Pain in Rats / 대한통증학회지

BACKGROUND: It has been known that melatonin is involved in the modulation of nociceptive transmission. However, the effect of melatonin administered spinally has not been examined. Therefore, we examined the effect of melatonin on the formalin-induced or thermal-induced nociception at the spinal level. METHODS: Intrathecal catheter was inserted into the subarachnoid space of male Sprague-Dawley rats. Pain was assessed by formalin test (induced by injection of 50microliter of a 5% formalin solution to the hindpaw) or Hot-Box test (induced by radiant heat application to the hindpaw). The effect of intrathecal melatonin was examined on flinching behavior in the formalin test or withdrawal response in Hot-Box test. RESULTS: Intrathecal melatonin produced a limited, but dose-dependent reduction of the flinching response during phase 1 and 2 in the formalin test. In addition, melatonin delivered at evening also decreased the flinching response in both phases of the formalin test. Melatonin restrictively increased the withdrawal latency in Hot-Box test. CONCLUSIONS: These results suggest that melatonin is active against the formalin- and thermal-induced nocicpetion at the spinal level, but the effect is limited.