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.