Incidence of newly developed postoperative low back pain with median versus paramedian approach for spinal anesthesia.

Background: The effects of anesthetic techniques on postdural puncture backache (PDPB) have not been specifically evaluated. The purpose of this study was to compare the incidence and severity of PDPB between median and paramedian techniques. Methods: Patients were randomized to receive spinal anesthesia by either a median (Group M, n = 50) or paramedian (Group P, n = 50) approach. We recorded each patient's personal number of puncture attempts, surgical position, and operation duration. We investigated the incidence and intensity of back pain 1 day, 1 week, and 1, 2, and 3 months postoperatively. Results: The overall incidence of PDPB was higher in the Group M (18/50, 36%) than in the Group P (8/50, 16%) (P = 0.023). Twenty-four hours after surgery, 8 patients in Group M and 6 patients in Group P complained of back pain. Seven days after the surgery, 16 patients in the Group M and 5 patients in the Group P complained of pain (P = 0.007). After 1 month, 5 patients in the Group M and 1 patient in the Group P complained of pain. Only one patient in each group complained of pain after 3 months. No significant differences were noted in NRSs between the groups during study period. Conclusions: The results of this study suggest that spinal anesthesia using the paramedian approach reduces the incidence of PDPB during the early postoperative period.

The role of inversely operating glutamate transporter in the paradoxical analgesia produced by glutamate transporter inhibitors.

Controlling extracellular glutamate level in a physiological range is important to maintain normal sensory transmission. Here, we investigated the paradoxical action of glutamate transporters in the rat formalin test to elucidate a possible role of inversely operating transporters in its analgesic mechanism. The effects of glutamate transporter inhibitor on formalin-induced pain behavior were examined. Then we performed a microdialysis study to clarify the differential change in extracellular glutamate concentration by intrathecal administration of transportable and non-transportable blockers. And we further investigated the mechanism pharmacologically via pretreatment with antagonists of various receptors and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Intrathecally-injected glutamate transporter inhibitors, non-transportable DL-threo-ß-benzyloxyaspartat (TBOA) and transportable trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC), produced paradoxical antinociception in the formalin test. In normal rats, inhibition of the glutamate transporter increased extracellular glutamate. In the formalin model rats, TBOA suppressed while t-PDC enhanced glutamate release. When tPDC was pretreated 30min prior to formalin injection, glutamate release was blocked. Blocking α-2 adrenergic receptors reversed the tPDC analgesia. Increased apoptosis was not apparent in the spinal dorsal horn of tPDC-treated rats compared to the control group. These data suggest that glutamate transporters in a formalin-induced pain state work in a reverse mode and can be blocked from releasing glutamate by TBOA and preloaded tPDC. The analgesic mechanism of TBOA may be related to the blockade of inversely operating transporter, and that of tPDC may be associated with the activation of noradrenergic neurotransmission but not with dorsal horn neurotoxicity.

Comparison of effects of intraoperative nefopam and ketamine infusion on managing postoperative pain after laparoscopic cholecystectomy administered remifentanil.

BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia and reduce the use of postoperative analgesics, it may cause opioid induced hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to determine whether intraoperative nefopam or ketamine, known being related on NMDA receptor, affects postoperative pain and OIH after continuous infusion of intraoperative remifentanil. METHODS: Fifty-four patients undergoing laparoscopic cholecystectomy were randomized into three groups. In the nefopam group (N group), patients received nefopam 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h. In the ketamine group (K group), patients received ketamine 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 3 µg/kg/min. The control group did not received any other agents except for the standard anesthetic regimen. Postoperative pain score, first time and number of demanding rescue analgesia, OIH and degrees of drowsiness/sedation scale were examined. RESULTS: Co-administrated nefopam or ketamine significantly reduced the total amount of intraoperative remifentanil and postoperative supplemental morphine. Nefopam group showed superior property over control and ketamine group in the postoperative VAS score and recovery index (alertness and respiratory drive), respectively. Nefopam group showed lower morphine consumption than ketamine group, but not significant. CONCLUSIONS: Both nefopam and ketamine infusion may be useful in managing in postoperative pain control under concomitant infusion of remifentanil. However, nefopam may be preferred to ketamine in terms of sedation.

Femoral nerve block for patient undergoing total knee arthroplasty: Prospective, randomized, double-blinded study evaluating analgesic effect of perineural fentanyl additive to local anesthetics.

BACKGROUND: The existence of peripheral opioid receptors and its effectiveness in peripheral nerve block remain controversial. The aim of this prospective, randomized, double-blinded study was to examine the analgesic effects of adding fentanyl to ropivacaine for continuous femoral nerve block (CFNB) using patient-controlled analgesia after total knee arthroplasty (TKA). METHODS: The patients were divided into 2 groups, each with n = 40 in ropivacaine (R) group and n = 42 in R with fentanyl (R + F) group. After operation, the patients in each group received R + F and R alone via a femoral nerve catheter, respectively. We assessed the visual analog scale (VAS) pain immediately before administration (baseline) and at 15, 30, and 60 minutes on postanesthesia care unit (PACU), and resting and ambulatory VAS score up to 24 hours. RESULTS: Overall, the average VAS scores in the R + F group were slightly lower than those of the R group. However, the VAS score differences between groups were not statistically significant, except for 30 minutes (P = 0.009) in PACU. R group showed higher supplemental analgesics consumption in average compared with R + F group, but not significant. CONCLUSION: Additional fentanyl did not show prominent enhancement of analgesic effect in the field of CFNB after TKA.

Effects of tianeptine on the development and maintenance of mechanical allodynia in a rat model of neuropathic pain.

We validate the analgesic efficacy of tianeptine by different administration routes and timing in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of orally administered tianeptine and pretreatment with tianeptine (intrathecally or intraperitoneally) on mechanical allodynia were assessed. Oral and preemptive intrathecal administration of tianeptine significantly increased the paw withdrawal threshold but preemptive intraperitoneal administration did not. Nevertheless, intraperitoneal pretreatment of tianeptine potentiated the antiallodynic effects of subsequently administered tianeptine. These findings suggest that tianeptine may be effective for preventing and treating neuropathic pain and that it can be used more widely in clinical pain practice.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain.

BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

A New Rat Model of Cisplatin-induced Neuropathic Pain.

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. METHODS: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. RESULTS: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. CONCLUSIONS: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

A Comparative Efficacy of Propacetamol and Ketorolac in Postoperative Patient Controlled Analgesia.

BACKGROUND: Ketorolac has been used as a postoperative analgesia in combination with opioids. However, the use of ketorolac may produce serious side effects in vulnerable patients. Propacetamol is known to induce fewer side effects than ketorolac because it mainly affects the central nervous system. We compared the analgesic effects and patient satisfaction levels of each drug when combined with fentanyl patient-controlled analgesia (PCA). METHODS: The patients were divided into two groups, each with n = 46. The patients in each group were given 60 mg of ketorolac or 2 g of propacetamol (mixed with fentanyl) for 10 minutes. The patients were then given 180 mg of ketorolac or 8 g of propacetamol (mixed with fentanyl and ramosetron) through PCA. We assessed the visual analogue pain scale (VAS) at the time point immediately before administration (baseline) and at 15, 30, and 60 minutes, and 24 hours after administration. Also, the side effects of each regimen and each patient's degree of satisfaction were assessed. RESULTS: There was a significant decline in the VAS score in both groups (P < 0.05). However, there were no significant differences in the VAS scores between the groups at each time point. Satisfaction scores between the groups showed no significant difference. CONCLUSIONS: The efficacy of propacetamol is comparable to that of ketorolac in postoperative PCA with fentanyl.

Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.

Delayed allergic reaction to secondary administrated epidural hyaluronidase.

We are reporting a rare case of a delayed hypersensitivity reaction caused by hyaluronidase allergy following a lumbar transforaminal epidural block. Using an intradermal skin test, we have provided evidence that the systemic allergic reaction resulted from hypersensitivity to hyaluronidase. To our knowledge, this is a rare case of a delayed hypersensitivity reaction to epidural hyaluronidase, comprised of an initial exposure to hyaluronidase with no subsequent allergic response in prior block followed by a subsequent delayed reaction to hyaluronidase during a second epidural block.

Epidural Infusion of Morphine and Levobupivacaine through a Subcutaneous Port for Cancer Pain Management.

BACKGROUND: To manage intractable cancer pain, an alternative to systemic analgesics is neuraxial analgesia. In long-term treatment, intrathecal administration could provide a more satisfactory pain relief with lower doses of analgesics and fewer side-effects than that of epidural administration. However, implantable drug delivery systems using intrathecal pumps in Korea are very expensive. Considering cost-effectiveness, we performed epidural analgesia as an alternative to intrathecal analgesia. METHODS: We retrospectively investigated the efficacy, side effects, and complications of epidural morphine and local anesthetic administration through epidural catheters connected to a subcutaneous injection port in 29 Korean terminal cancer patients. Patient demographic data, the duration of epidural administration, preoperative numerical pain rating scales (NRS), side effects and complications related to the epidural catheterization and the drugs, and the numerical pain rating scales on the 1st, 3rd, 7th and 30th postoperative days were determined from the medical records. RESULTS: The average score for the numerical pain rating scales for the 29 patients decreased from 7 ± 1.0 at baseline to 3.6 ± 1.4 on postoperative day 1 (P < 0.001). A similar decrease in pain intensity was maintained for 30 days (P < 0.001). Nausea and vomiting were the most frequently reported side effects of the epidural analgesia and two patients (6.9%) experienced paresthesia. CONCLUSIONS: Epidural morphine and local anesthetic infusion with a subcutaneous pump seems to have an acceptable risk-benefit ratio and allows a high degree of autonomy to patients with cancer pain.

Spinal noradrenergic modulation and the role of the alpha-2 receptor in the antinociceptive effect of intrathecal nefopam in the formalin test.

BACKGROUND: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. METHODS: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. RESULTS: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. CONCLUSIONS: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.

Epigallocatechin-3-gallate, a green tea catechin, protects the heart against regional ischemia-reperfusion injuries through activation of RISK survival pathways in rats.

Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3ß or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3ß, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3ß but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.

Effect-site concentration of remifentanil for blunting hemodynamic response to double lumen endobronchial intubation during target controlled infusion-total intravenous anesthesia using propofol with remifentanil.

BACKGROUND: This study was undertaken to determine the effect-site concentration of remifentanil for blunting hemodynamic responses to double lumen endobronchial intubation during target controlled infusion (TCI)-total intravenous anesthesia (TIVA) using 4.0 microg/ml of propofol with remifentanil. METHODS: Sixty patients (American society of anesthesiologists physical status classification 1 or 2) were randomly allocated according to the target effect-site concentration of remifentanil (R3.0: remifentanil 3.0 ng/ml; R3.5: remifentanil 3.5 ng/ml; R4.0: remifentanil 4.0 ng/ml). The effect-site concentration of propofol at loss of consciousness was recorded. Mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS) were recorded at just before remifentanil administration (baseline), at the time of target effect site concentration of remifentanil and propofol, at just before intubation and 1, 2, 3 min after intubation. RESULTS: MAP was significantly increased compared with baseline at 1, 2 min after intubation in R3.0, but was significantly decreased in R4.0. MAP of R3.5 was not different from the baseline after intubation. HR was significantly decreased compared with baseline at the time of target effect site concentration of propofol and immediate before intubation in R3.5 and R4.0. After intubation, HR was significantly increased compared with baseline at only 1 min after intubation and returned to the baseline in R3.0. However, HR was continuously decreased in R4.0. CONCLUSIONS: These findings suggest that effective target effect-site concentration of remifentanil for blunting hemodynamic responses to double lumen endotracheal intubation was 3.5 ng/ml during TCI-TIVA using 4.0 microgram/ml of propofol with remifentanil.