Jin Woo Shin

Mechanism of taxol‐induced apoptosis in human SKOV3 ovarian carcinoma cells

Taxol is extensively used clinically for chemotherapy of patients with ovarian, breast, and lung cancer. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. To determine the mechanism of action of taxol in ovarian cancer, we tested the effects of the drug, on the human ovarian carcinoma cell line, SKOV3. We observed that taxol‐induced apoptosis of these cells by phosphatidylserine (PS) externalization and DNA fragmentation. While treatment of cells with taxol resulted in bcl‐2 phosphorylation and mitochondrial depolarization, cytochrome c was not released and pro‐caspase‐3 was not activated. Treatment of SKOV3 cells with taxol, however, resulted in the translocation of AIF from the mitochondria to the nucleus via the cytosol. Taken together, these findings suggest that in SKOV3 cells, taxol induces caspase‐independent AIF‐dependent apoptosis.

Incidence of post-thoracotomy pain: a comparison between total intravenous anaesthesia and inhalation anaesthesia

OBJECTIVES Thoracotomy is one of the most painful surgical incisions. Little is known, however, about the effect of type of anaesthesia on chronic post-thoracotomy pain syndrome (CPTS). We therefore compared the incidence of CPTS after total intravenous anaesthesia (TIVA) and inhalation anaesthesia. METHODS Patients (n = 366) were prospectively randomized into two groups: Group I (n = 173) received TIVA (propofol + remifentanil) and Group II (n = 170) received inhalation anaesthesia with sevoflurane. We assessed acute pain on postoperative days 1, 3 and 5, and the prevalence of CPTS at 3 and 6 months using a numerical rating scale (NRS). RESULTS The prevalence of CPTS was significantly lower in patients receiving TIVA than in those receiving inhalation anaesthesia at 3 months (38.2% versus 56.5%, P = 0.001) and at 6 months (33.5% versus 50.6%, P = 0.002), respectively. Moreover, allodynia-like pain was significantly less common in the TIVA group at 3 (P = 0.021) and 6 months (P = 0.032). NRS score of acute pain, however, did not differ significantly between the two groups. CONCLUSIONS TIVA with propofol and remifentanil may reduce the incidence of CPTS at 3 and 6 months.

Protective effect of isoflurane anesthesia on noise-induced hearing loss in mice.

Hypothesis/Objectives: To examine the protective effect of general anesthesia with isoflurane against noise‐induced hearing loss in mice.

Ultrasound-guided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Patient with Intractable Hiccup

Persistent and intractable hiccups (with respective durations of more than 48 hours and 1 month) can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. The conventional treatments for hiccups are either non-pharmacological, pharmacological or a nerve block treatment. Pulsed radiofrequency lesioning (PRFL) has been proposed for the modulation of the excited nervous system pathway of pain as a safe and nondestructive treatment method. As placement of the electrode in close proximity to the targeted nerve is very important for the success of PRFL, ultrasound appears to be well suited for this technique. A 74-year-old man suffering from intractable hiccups that had developed after a coronary artery bypass graft and had continued for 7 years was referred to our pain clinic. He had not been treated with conventional methods or medications. We performed PRFL of the phrenic nerve guided by ultrasound and the hiccups disappeared.

Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats

Background:  Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N‐methyl‐d‐aspartate (NMDA) receptor‐gated ion channels, which are usually blocked by magnesium plugs. As magnesium‐deficient rats develop a mechanical hyperalgesia and intrathecal or intraperitoneal magnesium suppresses neuropathic pain, the magnesium concentrations in serum and cerebrospinal fluid may be altered in neuropathic pain. We therefore compared the magnesium concentrations in serum and cerebrospinal fluid of neuropathic rats with those in injured rats without symptoms of neuropathic pain and normal rats.

Tumor Necrosis Factor-alpha and Apoptosis Following Spinal Nerve Ligation Injury in Rats

Background Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-α and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-α protein levels in the L5-6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-α protein levels were increased in the DRG in rats that had undergone SNL (12.7 ± 3.2 pg/100 µg, P < 0.001) when compared with naïve rats (4.1 ± 1.4 pg/100 µg). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naïve rats (P < 0.001, P < 0.05, respectively). Conclusions SNL injury produces mechanical and cold allodynia, as well as TNF-α elevation and apoptosis in the DRG.

A Novel Balloon-Inflatable Catheter for Percutaneous Epidural Adhesiolysis and Decompression

Epidural adhesions cause pain by interfering with the free movement of the spinal nerves and increasing neural sensitivity as a consequence of neural compression. To remove adhesions and deliver injected drugs to target sites, percutaneous epidural adhesiolysis (PEA) is performed in patients who are unresponsive to conservative treatments. We describe four patients who were treated with a newly developed inflatable balloon catheter for more effective PEA and relief of stenosis. In the present patients, treatments with repetitive epidural steroid injection and/or PEA with the Racz catheter or the NaviCath did not yield long-lasting effects or functional improvements. However, PEA and decompression with the inflatable balloon catheter led to maintenance of pain relief for more than seven months and improvements in the functional status with increases in the walking distance. The present case series suggests that the inflatable balloon catheter may be an effective alternative to performing PEA when conventional methods fail to remove adhesions or sufficiently relieve stenosis.

Protective effects of propofol against hydrogen peroxide-induced oxidative stress in human kidney proximal tubular cells

Background We investigated the protective effects of propofol in the HK-2 cell line of human kidney proximal tubular cells against hydrogen peroxide (H2O2)-induced oxidative stress. Methods After pretreatment with different concentrations of propofol (0 µM, 10 µM, 25 µM and 50 µM) for 30 minutes, HK-2 cells were exposed to 8 mM H2O2 for 4 hours. Cell death was assessed by measuring the percentage of lactate dehydrogenase (LDH) release and by counting viable cells. The nature of cell death was assessed by doubles-taining cells with fluorescein isothiocyanate-labeled Annexin V and propidium iodide, and then analyzing the cells using flow cytometry. Results After exposure to 8 mM H2O2 for 4 hours, the percentage of LDH release was 45.1 ± 4.2% and the number of viable HK-2 cells was 5.2 ± 6.0%. Pretreatment with propofol suppressed H2O2-induced LDH release in a concentration-dependent manner, reducing the percentage of LDH release to 38.1 ± 5.6%, 33.5 ± 6.3%, and 26.2 ± 3.8% of the controls at 10 µM, 25 µM and 50 µM propofol, respectively. Numbers of viable cells increased following propofol pretreatment, with 11.4 ± 10.9%, 19.5 ± 16.1%, and 32.4 ± 23.3% cell survival rates after pretreatment with 10 µM, 25 µM and 50 µM propofol, respectively. Analyses of flow cytometry showed that the propofol pretreatment decreased the percentage of necrotic and late apoptotic cells. Conclusions Propofol protects HK-2 human kidney proximal tubular cells against H2O2-induced oxidative stress.

Effect of Perioperative Perineural Injection of Dexamethasone and Bupivacaine on a Rat Spared Nerve Injury Model

Background Neuropathic pain resulting from diverse causes is a chronic condition for which effective treatment is lacking. The goal of this study was to test whether dexamethasone exerts a preemptive analgesic effect with bupivacaine when injected perineurally in the spared nerve injury model. Methods Fifty rats were randomly divided into five groups. Group 1 (control) was ligated but received no drugs. Group 2 was perineurally infiltrated (tibial and common peroneal nerves) with 0.4% bupivacaine (0.2 ml) and dexamethasone (0.8 mg) 10 minutes before surgery. Group 3 was infiltrated with 0.4% bupivacaine (0.2 ml) and dexamethasone (0.8 mg) after surgery. Group 4 was infiltrated with normal saline (0.2 ml) and dexamethasone (0.8 mg) 10 minutes before surgery. Group 5 was infiltrated with only 0.4% bupivacaine (0.2 ml) before surgery. Rat paw withdrawal thresholds were measured using the von Frey hair test before surgery as a baseline measurement and on postoperative days 3, 6, 9, 12, 15, 18 and 21. Results In the group injected preoperatively with dexamethasone and bupivacaine, mechanical allodynia did not develop and mechanical threshold forces were significantly different compared with other groups, especially between postoperative days 3 and 9 (P < 0.05). Conclusions In conclusion, preoperative infiltration of both dexamethasone and bupivacaine showed a significantly better analgesic effect than did infiltration of bupivacaine or dexamethasone alone in the spared nerve injury model, especially early on after surgery.

Effect of Ethyl Pyruvate on Paclitaxel-Induced Neuropathic Pain in Rats

Background Although paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration. Methods Rats were randomly divided into 3 groups: 1) a control group, which received only vehicle; 2) a paclitaxel group, which received paclitaxel; and 3) an EP group, which received EP after paclitaxel administration. Mechanical allodynia was tested before and at 7 and 14 days after final paclitaxel administration. Fourteen days after paclitaxel treatment, DRG apoptosis was determined by activated caspase-3 immunoreactivity (IR). Results Post-treatment with EP did not significantly affect paclitaxel-induced allodynia, although it tended to slightly reduce sensitivities to mechanical stimuli after paclitaxel administration. After paclitaxel administration, an increase in caspase-3 IR in DRG cells was observed, which was co-localized with NF200-positive myelinated neurons. Post-treatment with EP decreased the paclitaxel-induced caspase-3 IR. Paclitaxel administration or post-treatment with EP did not alter the glial fibrillary acidic protein IRs in DRG cells. Conclusions Inhibition of apoptosis in DRG neurons by EP may not be critical in paclitaxel-induced mechanical allodynia.