Tomohiro Soga

Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats

The neurosteroid allopregnanolone (AP) influences the excitability of the central nervous system by acting as a positive allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors. Here, we investigated the role of AP and its therapeutic potential in rats that showed hyperalgesic behavior after undergoing spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of rats that underwent SNL were greater than the corresponding levels in control animals. More importantly, spinal AP levels in hyperalgesic rats were lower than those in the rats that did not develop hyperalgesia following SNL; in contrast, brain AP levels were comparable among these groups. No differences in serum AP levels were observed among the groups. In addition, intrathecal exogenous administration of AP showed the antihyperalgesic effects in hyperalgesic rats after SNL. These findings suggest that changes in spinal AP biosynthesis are involved in the pathogenesis of neuropathic pain following peripheral nerve injury, and pharmacological manipulation of this phenomenon may provide a potential therapeutic target for neuropathic pain.

The effects of intravenous fosaprepitant and ondansetron for the prevention of postoperative nausea and vomiting in neurosurgery patients: a prospective, randomized, double-blinded study.

The incidence of postoperative nausea and vomiting (PONV) is 30–50% after surgery. PONV occurs frequently, especially after craniotomy. In this study, we investigated the preventive effects on PONV in a randomized study by comparing patients who had been administered fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, or ondansetron intravenously. Sixty-four patients undergoing craniotomy were randomly allocated to receive fosaprepitant 150 mg i.v. (NK1 group, n = 32) or ondansetron 4 mg i.v. (ONS group, n = 32) before anesthesia. The incidence of vomiting was significantly less in the NK1 group, where 2 of 32 (6%) patients experienced vomiting compared to 16 of 32 (50%) patients in the ONS group during the first 24 and 48 hours following surgery. Additionally, the incidence of complete response (no vomiting and no rescue antiemetic use) was significantly higher in the NK1 group than in the ONS group, and was 66% versus 41%, respectively, during the first 24 hours, and 63% versus 38%, respectively, during the first 48 hours. In patients undergoing craniotomy, fosaprepitant is more effective than ondansetron in increasing the rate of complete response and decreasing the incidence of vomiting at 24 and 48 hours postoperatively.

The involvement of the neurosteroid allopregnanolone in the antihyperalgesic effect of paroxetine in a rat model of neuropathic pain

Paroxetine increases the levels of neurosteroids, such as allopregnanolone (AP), that influence the excitability of the central nervous system by positive allosteric modulation of &ggr;-aminobutyric acid type A receptors. Here, we investigated the role of AP synthesis on the paroxetine-induced antihyperalgesic effect in a rat model of neuropathic pain induced by lumbar spinal nerve ligation (SNL). Subcutaneous administration of paroxetine in SNL rats, dose-dependently decreased the probability of hyperalgesic response and increased AP levels in the spine but not in either brain or serum. Concomitant treatment with an inhibitor of the AP-synthesizing enzyme, finasteride, attenuated the paroxetine-induced antihyperalgesic effect as well as the paroxetine-induced increase in spinal AP levels. Intrathecal injection of exogenous AP mimicked the analgesic effects of paroxetine in vehicle-treated SNL rats, whereas no additional analgesic effects were observed in paroxetine-treated SNL rats. Our findings suggest that the antihyperalgesic effect of paroxetine in a rat neuropathic pain model is AP-mediated. These results also suggest that pharmacological-based therapies targeting AP synthesis might be a promising treatment for neuropathic pain.

Impact of newly developed, next-generation artificial endocrine pancreas.

BACKGROUND Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). METHODS Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latters fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. RESULTS Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. CONCLUSION The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.

Successful treatment of mixed (mainly cancer) pain by tramadol preparations

The patient, a 70-year-old Japanese woman diagnosed with parotid gland cancer, underwent wide excision and reconstruction (facial nerve ablation, nerve transposition). At 1 month after the surgery, she was brought to our hospitals pain medicine department because her postoperative pain and cancer-related pain were poorly controlled. She had already been prescribed a tramadol (37.5 mg)/acetaminophen (325 mg) combination tablet (5 tablets/day). However, in addition to the continuous pain in her face and lower limbs, she was troubled by a trigeminal neuralgia-like prominence ache. Because this pain could not be controlled by an increase to eight combination tablets per day, we switched her medication to a tramadol capsule. At 11 months post-surgery, we then switched her medication to an orally disintegrating tramadol tablet to improve medication adherence of the drug. From 14 months post-surgery, the patient also used a sustained-release tramadol preparation, and she was then able to sleep well. Her current regimen is an orally disintegrating sustained-release tablet combination (total 300 mg tramadol) per day, and she achieved sufficient pain relief. Because tramadol is not classified as a medical narcotic drug, it widely available and was shown here to be extremely useful for the treatment of our patients mixed (mainly cancer) pain. J. Med. Invest. 64: 311-312, August, 2017.