SR 57227A, a serotonin type-3 receptor agonist, as a candidate analgesic agent targeting nociplastic pain.

Pain is influenced by various factors, such as fear, anxiety, and memory. We previously reported that pain-like behaviors in mice can be induced by environmental cues in which a pain stimulus was previously presented, and that pain was reduced using fentanyl (an opioid). Although opioid analgesics are currently used to treat persistent pain, their inappropriate use causes a significant number of deaths in the United States. Thus, alternative medicines to opioids are needed. Here, we reported that SR 57227A, a serotonin type-3 receptor agonist, significantly reduced pain-like behaviors. The number of c-Fos positive cells increased by environmental cues in PFC was decreased by SR 57227A. Moreover, SR 57227A reduced pain-like behaviors of the formalin test, and restored reductions in paw withdrawal thresholds by acidic saline intramuscular injection and sciatic nerve ligation. Unlike opioids, SR 57227A induced no preference behaviors as measured by the conditioned place preference test. These data suggested that SR 57227A is an effective alternative pain reliever to opioids that targets chronic pain.

A new rocuronium formulation not causing vascular pain in a flexor reflex model of anesthetized rats.

PURPOSE: Intravenous administration of the brand formulation of rocuronium bromide, currently used as a muscle relaxant, has been associated with vascular pain accompanied by withdrawal movements of the arm and wrist. The purpose of this study was to identify the cause of vascular pain induced by the brand formulation and to develop a new rocuronium formulation, not causing vascular pain, using a vascular pain-evoked flexor reflex response model of anesthetized rats. METHODS: A rat flexor reflex model, monitored by electromyography, was used to evaluate a flexor reflex response as the index of vascular pain. A catheter for drug administration was inserted into the superficial caudal epigastric artery. A needle electrode was inserted into a muscle in the femoral area to obtain an electromyogram (EMG) value. The integrated EMG values obtained after the administration of each test drug were compared to the baseline value and quantified. RESULTS: The acetate buffer contained in the solvent could cause flexor reflex response. Furthermore, the flexor reflex response increased in an acid concentration-dependent manner. Based on these results, we prepared a new rocuronium formulation using a low-acid-concentration buffer solution and found that it decreased the integrated EMG value in the rat model. The integrated EMG value acquired using the brand formulation was reduced by pretreatment with the TRPA1 channel inhibitor. CONCLUSION: Our findings suggest that the high acid concentration in the brand formulation buffer solution is the cause of vascular pain. The rocuronium formulation developed using a low-acid-concentration buffer solution might help eliminate vascular pain in the clinic.

Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0 mouse melanoma cells.

In a previous study performed by our group, we demonstrated that the water extract of Cordyceps sinensis (WECS) significantly prevented tumor metastasis from the spleen to the liver, using B16-F0 mouse melanoma cells as a model. In this study, we investigated the anti-metastatic activity of cordycepin (3'-deoxyadenosine), one of the components of WECS, using an identical model of mice injected with B16-F0 cells into the spleen. All mice inoculated with B16-F0 cells died due to liver metastases via the portal vein from the spleen. Control mice not administered cordycepin exhibited higher serum levels of alanine aminotransferase (ALT) due to damage to the liver by metastasized B16-F0 cells from the spleen, and survival times ranged from 17 to 22 days after tumor inoculation. Cordycepin was intraperitoneally administered to mice, and resulted in significantly lower serum ALT levels and longer survival times than those observed in control mice. Taken together, these results indicate that cordycepin may be the active ingredient in C. sinensis exerting an anti-metastatic effect, and may be a potential candidate anti-metastatic agent.

Inhibitory effect of Cordyceps sinensis on experimental hepatic metastasis of melanoma by suppressing tumor cell invasion.

We investigated the anti-metastatic activity of a water extract of Cordyceps sinensis (WECS) using a model of mice injected with B16-F0 mouse melanoma cells into the spleen. WECS administered intraperitoneally reduced the number of metastatic surface nodules of B16-F0 cells in the liver of C57BL/6Cr mice in a dose-dependent manner, and significantly prolonged their survival. To identify the mechanism of the anti-metastatic effect of WECS, we examined its effects on hepatocyte growth factor (HGF)-accelerated invasion of B16-F0 cells using a chemo-invasion assay in vitro. As a result, WECS reduced HGF-accelerated B16-F0 cell invasion in a concentration-dependent manner. These findings suggest that WECS exerts an anti-metastatic action, in part by inhibiting the HGF-accelerated tumor invasiveness of mouse melanoma cells.