Background and objectives This randomized, controlled, double-blind trial compared the effectiveness of levobupivacaine delivery of a programmed intermittent paravertebral bolus with a continuous paravertebral infusion. Methods Thirty-two consecutively enrolled patients who underwent unilateral video-assisted thoracic surgery were randomized to receive either a programmed intermittent paravertebral bolus of 10 mL of 0.2% levobupivacaine every 2 hours (Bolus group, n=16) or a continuous paravertebral infusion of 0.2% levobupivacaine at 5 mL/hour (Infusion group, n=16) after the operation. Postoperatively, after injection of 20 mL of 0.25% levobupivacaine through the paravertebral catheter, a mechanical infusion pump was set depending on the assigned group. The primary efficacy outcome was the number of anesthetized dermatomes 24 hours after the initial bolus of levobupivacaine. The secondary efficacy outcomes included the number of anesthetized dermatomes at other time points, pain at rest and coughing, additional analgesic use and patient acceptance of the analgesic technique. Arterial levobupivacaine concentration was measured to ensure safety. P<0.05 was considered statistically significant. Results The mean (95% CI) number of anesthetized dermatomes 24 hours after the initial bolus of levobupivacaine was significantly larger among subjects receiving programmed intermittent bolus (n=16) compared with those receiving continuous infusion (n=16; 6.8 (5.7–7.9) vs 3.1 (2.0–4.2); p<0.001). The arterial levobupivacaine concentration did not reach a toxic level. Conclusions The programmed intermittent paravertebral bolus of levobupivacaine provided a wider dermatomal spread of sensory block than continuous paravertebral infusion with an identical hourly dose of levobupivacaine. Trial registration number UMIN000022532.

BACKGROUND: Ultrasound-guided supraclavicular brachial plexus block carries a risk for puncture of vascular structures. In this study, we determined the frequency with which the transverse cervical artery (TCA) and the dorsal scapular artery (DSA) are detected by ultrasound evaluation at 3 probe positions during supraclavicular block. METHODS: Ultrasound examinations of the supraclavicular region were performed in 53 healthy adult volunteers. Ultrasound images of the supraclavicular region were acquired at 3 probe positions: position A (the brachial plexus and the subclavian artery both lying on the first rib); position B (the brachial plexus on the first rib; the artery on the pleura); and position C (the brachial plexus between the anterior and middle scalene muscles). The primary outcome variables were the frequencies with which TCA and DSA were detected by 2-dimensional and color Doppler imaging at 3 specified probe positions. RESULTS: One hundred six supraclavicular regions were examined in 53 subjects. The subclavian artery was detected in all subjects. TCA was more often detected than DSA, 94 (88.7%, 95% confidence interval [CI] 80.7%–93.8%) and 36 (34%, 95% CI 25.3%–43.9%) of 106 scans, respectively (McNemar P value <0.001). TCA was detected in 2 (1.9%, 95% CI 0.3%–7.3%), 31 (29.2%, 95% CI 20.9%–38.9%), and 61 (57.5%, 95% CI 47.5%–66.9%) of scans at probe positions A, B, and C, respectively, whereas DSA was detected in 3 (2.8%, 95% CI 0.7%–8.6%), 23 (21.7%, 95% CI 14.5%–30.9%), and 10 (9.4%, 95% CI 4.8%–17.0%) of scans at probe positions A, B, and C, respectively. Thus, the TCA and DSA were less likely to be present with probe position A (all P < 0.001). CONCLUSION: TCA was more often detected than DSA in the vicinity of the brachial plexus in the supraclavicular region. Both TCA and DSA were least likely to be present in probe position A. Color Doppler, particularly for probe position A, may help to reduce the risk for inadvertent vascular puncture during ultrasound-guided supraclavicular block.

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i); however, carboplatin pretreatment enhanced the increase in [Ca²⁺]_i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca²⁺]_i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca²⁺]_i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

Zoledronic acid (ZOL), a third-generation bisphosphonate, inhibits bone resorption, as well as exhibiting direct antitumor activity. To date, however, the combined effects of ZOL and ionizing radiation (IR) have not been assessed in patients with soft tissue sarcoma. We have, therefore, assessed the combined effects of ZOL and IR in fibrosarcoma cells. HT1080 fibrosarcoma cells were treated with ZOL and/or IR, together or sequentially and the antitumor effects were assessed. We found that ZOL significantly enhanced IR-induced apoptosis, especially when cells were treated with ZOL followed by IR. We, therefore, assessed the detailed mechanism of sequential treatment with ZOL and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of ZOL. However, the levels of expression of Akt, ERK1/2 and NF-κB proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of ZOL, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS). These results suggest that the combination of ZOL with IR may be beneficial in treating patients with soft tissue sarcoma.