Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Background@#This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. @*Methods@#The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. @*Results@#Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. @*Conclusions@#SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Background@#This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. @*Methods@#The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. @*Results@#Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. @*Conclusions@#SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

Background@#This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). @*Methods@#Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. @*Results@#The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (p < 0.05). The expressions of p65, proinflammatory cyto kines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (p < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. @*Conclusions@#Gabexate mesilate increased PWT after SNL and attenuate the pro gress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.

Antinociceptive effects of intrathecal cimifugin treatment: a preliminary rat study based on formalin test

Background@#Cimifugin is one of the components of the root of Saposhnikovia divaricata. The extract derived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesic effect of intrathecal cimifugin in the formalin test. @*Methods@#Male Sprague–Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 μg, 300 μg, and 1,000 μg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 values were calculated via linear regression. @*Results@#Intrathecal cimifugin significantly reduced the flinch response in both phases of the formalin test. Significant antinociceptive effects of cimifugin were found with the dose of 300 μg in phase 1 and the dose of 100 μg in phase 2. The ED50 value (95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8–1,342.8) μg during phase 1 and 1,242.8 (42.0–48,292.5) μg during phase 2. @*Conclusions@#Intrathecal cimifugin has an antinociceptive effect against formalin-induced pain. Cimifugin has an anti-inflammatory effect at low concentrations, and non-inflammatory analgesic effect at higher concentrations.

Effect of sec-O-glucosylhamaudol on mechanical allodynia in a rat model of postoperative pain / 대한통증학회지

BACKGROUND: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. METHODS: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG (10 μg, 30 μg, 100 μg, and 300 μg) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG 300 μg in order to assess the involvement of SOG with an opioid receptor. The protein levels of the δ-opioid receptor, κ-opioid receptor, and μ-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. RESULTS: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of 300 μg at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was 191.3 μg (95% confidence interval, 102.3–357.8). The antinociceptive effects of SOG (300 μg) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. CONCLUSIONS: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

Autophagy: Can It be a New Experimental Research Method of Neuropathic Pain?

No abstract available.

Curcumin, COX-2, and Protein p300/CBP / 대한통증학회지

No abstract available.

Curcumin, COX-2, and Protein p300/CBP

No abstract available.

Palonosetron for postoperative nausea and vomiting after gynecological laparoscopic surgery: Comparison of its effect on sevoflurane vs desflurane vs total intravenous anesthesia

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most common complications after gynecological laparoscopic surgery and it appears more frequently after use of inhalation anesthetics than total intravenous anesthesia (TIVA). Palonosetron was introduced as a new-generation potent antiemetic agent, which may reduce PONV more effectively than previous drugs. The aim of this study was to evaluate whether palonosetron could prevent PONV after gynecological laparoscopic surgery, regardless of the anesthetic technique employed. METHODS: Seventy-three patients scheduled for gynecological laparoscopic surgery were randomly assigned into 3 groups according to the anesthetic agent employed (group 1: inhalation anesthesia with desflurane, group 2: inhalation anesthesia with sevoflurane, group 3: total intravenous anesthesia with propofol and remifentanil). Palonosetron 0.075 mg was administered intravenously before the induction. Opioids were not used for postoperative pain control. The incidences of nausea, vomiting and side effects were recorded from 2 hr upto 48 hr, postoperatively. RESULTS: There were no significant differences in the incidence of PONV, severity of nausea, and the use of rescue antiemetics among the groups, throughout the observation. No differences were observed in the adverse side effects among the groups. CONCLUSIONS: Palonosetron decreased the incidence of PONV after gynecological laparoscopic surgery to a similar level, regardless of the anesthetic technique.

Effect on thermoregulatory responses in patients undergoing a tympanoplasty in accordance to the anesthetic techniques during PEEP: a comparison between inhalation anesthesia with desflurane and TIVA / 대한마취과학회지

BACKGROUND: It has been known that positive end-expiratory pressure (PEEP) increases the vasoconstriction threshold by baroreceptor unloading. We compared the effect on the thermoregulatory responses according to anesthetic techniques between an inhalation anesthesia with desflurane and a total intravenous anesthesia (TIVA) with propofol and reminfentanil when PEEP was applied in patients undergoing tympanoplasty. METHODS: Forty-six patients with a scheduled tympanoplasty were enrolled and the patients were divided in two study groups. Desflurane was used as an inhalation anesthetic in group 1 (n = 22), while TIVA with propofol and remifentanil was used in group 2 (n = 24). PEEP was applied by 5 cmH2O in both groups and an ambient temperature was maintained at 22-24degrees C during surgery. The core temperature and the difference of skin temperature between forearm and fingertip were monitored for about 180 minutes before and after the induction of general anesthesia. RESULTS: The final core temperature was significantly higher in group 2 (35.4 +/- 0.7degrees C) than in group 1 (34.9 +/- 0.5degrees C). Peripheral thermoregulatory vasoconstriction was found in 5 subjects (23%) in group 1 and in 21 subjects (88%) in group 2. The time taken for reaching the thermoregulatory vasoconstriction threshold was 151.4 +/- 19.7 minutes in group 1 and 88.9 +/- 14.4 minutes in group 2. CONCLUSIONS: When PEEP will be applied, anesthesia with TIVA may have more advantages in core temperature preservation than an inhalation anesthesia with desflurane.

The Effect of Urinary Trypsin Inhibitor Against Neuropathic Pain in Rat Models

BACKGROUND: Nerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain. METHODS: Neuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the 5th day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the 5th day after SNL. RESULTS: The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05). CONCLUSIONS: Ulinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

Effects of Palonosetron, a 5-HT3 Receptor Antagonist, on Mechanical Allodynia in a Rat Model of Postoperative Pain

BACKGROUND: 5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. METHODS: An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 microg intrathecally; 0.5 microg intraplantarly) was administered and the thresholds were observed for 4 hours. RESULTS: Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 microg and 0.1 microg) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 microg) also did not change the paw withdrawal threshold. CONCLUSIONS: Intrathecal and intraplantar palonosetron (0.5 microg) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.

Clinical Experience of Symptomatic Sacral Perineural Cyst

Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic. Symptomatic sacral perineural cysts are uncommon but sometimes require surgical treatment. A 69-year-old male presented with pain in the buttock. He was diagnosed as having a sacral cyst with magnetic resonance imaging. For the nonoperative diagnosis and treatment, caudal peridurography and block were performed. After the treatment, the patient's symptom was relieved. We suggest a caudal peridural block is effective in relieving pain from a sacral cyst.

The effect of low dose ketamine and priming of cisatracurium on the intubating condition and onset time of cisatracurium / 대한마취과학회지

BACKGROUND: Both ketamine and priming may accelerate the onset time of neuromuscular blocking agents. We investigate the effect of low dose ketamine and cisatracurium priming on the intubating condition and onset time of cisatracurium. METHODS: After Institutional Review Board approval, 120 consecutive patients undergoing general anesthesia were randomly assigned to one of 4 groups. All patients were injected one of normal saline (group C), cisatracurium 0.01 mg/kg (group P), ketamine 0.5 mg/kg (group K) and combination of cisatracurium 0.01 mg/kg, and ketamine 0.5 mg/kg (group PK) diluted into a 5 ml solution, followed 3 minutes later by cisatracurium 0.15 mg/kg in group C and K, and 0.14 mg/kg cisatracurium in priming group. Onset time was recorded the electromyographical responses using single twitch and intubating conditions were evaluated at 60 seconds after cisatracurium administration. RESULTS: The mean onset time was most significantly accelerated in Group PK and was also significantly more accelerated in Group P and K compared with Group C (P < 0.008). It was 112.7 +/- 13.2, 91.4 +/- 17.9, 84.9 +/- 12.7 and 76.4 +/- 8.3 seconds in Group C, P, K, and PK, respectively. Intubating conditions were significantly improved in Group P, K and PK than Group C (P < 0.008). Especially, Group PK showed most significant improvement of intubating conditions. CONCLUSIONS: The combination of the low dose ketamine and cisatracurium priming accelerated the onset time and was improved the intubating conditions.

AKAP12 regulates vascular integrity in zebrafish

The integrity of blood vessels controls vascular permeability and extravasation of blood cells, across the endothelium. Thus, the impairment of endothelial integrity leads to hemorrhage, edema, and inflammatory infiltration. However, the molecular mechanism underlying vascular integrity has not been fully understood. Here, we demonstrate an essential role for A-kinase anchoring protein 12 (AKAP12) in the maintenance of endothelial integrity during vascular development. Zebrafish embryos depleted of akap12 (akap12 morphants) exhibited severe hemorrhages. In vivo time-lapse analyses suggested that disorganized interendothelial cell-cell adhesions in akap12 morphants might be the cause of hemorrhage. To clarify the molecular mechanism by which the cell-cell adhesions are impaired, we examined the cell-cell adhesion molecules and their regulators using cultured endothelial cells. The expression of PAK2, an actin cytoskeletal regulator, and AF6, a connector of intercellular adhesion molecules and actin cytoskeleton, was reduced in AKAP12-depleted cells. Depletion of either PAK2 or AF6 phenocopied AKAP12-depleted cells, suggesting the reduction of PAK2 and AF6 results in the loosening of intercellular junctions. Consistent with this, overexpression of PAK2 and AF6 rescued the abnormal hemorrhage in akap12 morphants. We conclude that AKAP12 is essential for integrity of endothelium by maintaining the expression of PAK2 and AF6 during vascular development.

AKAPDB: A-Kinase Anchoring Proteins Database

A-kinase-anchoring proteins (AKAPs) are scaffold proteins which compartmentalize protein kinase A (PKA, cAMP-dependent protein kinase) and other enzymes to specific subcellular sites. The spatiotemporal control of these enzymes by AKAPs is important for cellular function like cell growth and development etc. Hence, it is important to understand the basic function of AKAPs and their functional domains. However, diverse names, function, cellular localizations and many members of AKAPs increase difficulties when researchers search appropriate AKAPs for their experimental purpose. Nevertheless, there was no previous AKAPs-related database regardless of their important cellular functions and difficulty of finding appropriate AKAPs. So, we developed AKAPs database (AKAPDB), which contains their sequence information, functions and other information derived from prediction programs and other databases. Therefore, we propose that AKAPDB can be an important tool to researchers in the related fields. AKAPDB is available via the internet at http://plaza3.snu.ac.kr/akapdb/

Foot Necrosis Following Percutaneous Cannulation of the Dorsalis Pedis Artery: A Case Report / 대한구급학회지

Arterial canuulation is generally used to monitor blood pressure and sample blood for gas analysis. Radial and dorsalis pedis arteries are commonly used for arterial cannulation. It is a simple, safe, and uncomplicated procedure, but some complications have been reported, including bleeding, hematoma, infection, pseudoaneurysm, and thromboembolism. Although thromboembolism is not common, it could be serious because it can lead to digital ischemia and necrosis. We present a case of foot necrosis following dorsalis pedis artery cannulation in a 65-year-old patient who underwent small bowel resection.

Effect of tramadol on bispectral index during anesthesia with desflurane / 대한마취과학회지

BACKGROUND: This study is aimed to investigate the effect of tramadol on the bispectral index (BIS) during anesthesia with desflurane. METHODS: One hundred fifty adults, ASA class 1 and 2 patients, scheduled for general anesthesia for elective surgical procedures were included in this study. None of the patients were premedicated and anesthesia was induced with propofol 2 mg/kg and maintained with air-oxygen (FiO2 0.5) and desflurane, adjusted to keep the BIS between from 50 and 60. Forty minutes before completing surgery, the subjects were randomly allocated into 3 groups to receive saline (control group), tramadol 1.5 mg/kg (T1 group) or 3.0 mg/kg (T2 group) intravenously. Hemodynamics and BIS values were then recorded every 5 minutes until completion of the operation, during which time the concentrations of desflurane were not modified. RESULTS: The mean BIS values after tramadol administration weren't significantly different from the control group throughout the period of observation. No significant changes in the hemodynamics were noted, except systolic and diastolic arterial blood pressure in the T1 and T2 groups significantly increased in the first 5 minutes after the tramadol injection. CONCLUSIONS: The results indicate that the administration of tramadol while maintaining anesthesia with desflurane, adjusted to keep the BIS between 50 and 60, does not modified BIS values. So, we propose that tramadol can be safely administered as an immediate postoperative analgesia without concern about intra-operative awareness.

The effects of intrathecal fentanyl for spinal anesthesia in lower extremity surgery / 대한마취과학회지

BACKGROUND: Intrathecal opioids in combination with bupivacaine has been shown to provide adequate sensory blockade and early recovery from spinal anesthesia. This study was investigated the added effects of intrathecal fentanyl 10 microgram to bupivacaine for spinal anesthesia. METHODS: Sixty patients undergoing lower extremity surgery were into three groups. Group I received bupivacaine 10 mg (0.5%), gruop II received bupivacaine 5 mg with normal saline 1 ml, and group III received bupivacaine 5 mg with fentanyl 10 microg and normal saline 0.8 ml. RESULTS: There was no significant difference between group I and group III in the peak level and duration of sensory block. But the intensity of motor blockade was decreased in group III compared with group I and side effects of spinal anesthesia with local anesthetics was decreased in group III compared with group I. In Group II, 7 patients were complained the pain during surgery. CONCLUSIONS: Intrathecal fentanyl 10 microgram with bupivacaine 5 mg on spinal blockade provide reliable anesthesia for lower extremity surgery.

Spontaneous Regression of a Radiculopathic Cervical Herniated Disc following Non-surgical Treatment: 3 case reports / 대한통증학회지

The spontaneous regression of herniated cervical discs is not a well established phenomenon. However, we encountered the 3 cases of spontaneous regression of severe radiculopathic herniated cervical discs that were treated using a non-surgical method. Each of the patients were treated with a combination of manipulation, dry needling and analgesics. In each case, the symptoms improved within 12 months of treatment and magnetic resonance imaging (MRI) conducted at that time revealed marked regression of the herniated disc in all cases. These cases provide additional examples of spontaneous regression of herniated cervical discs documented by MRI following non-surgical treatment.