Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model

BackgroundTo identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn.MethodsIn experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan\u27s surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining.ResultsIn experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group.ConclusionsSystemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management

Effects of Neostigmine and Sugammadex on QT Interval and QT Dispersion

Dispersion of QT dispersion(QTD)in 12-lead electrocardiogram is a useful index for assessment of ventricular arrhythmia risk and cardiovascular event. To determine the effects of reversal of nondepolarizing neuromuscular blockade on cardiovascular event, we evaluated the QT interval QTD after reversal of the neuromuscular blockade by neostigmine or sugammadex.After obtaining the approval of the ethics committee of Dokkyo Medical University Hospital, 40 patients with ASA physical status I or II were allocated to following two groups. Patients in the groups N(n=16)and S(n=15)received combination of neostigmine(40?μg/kg)and atropine(20?μg/kg)or sugammadex(2?mg/kg)as a reversal of neuromuscular blockade after the operation under 1% sevoflurane anesthesia, respectively. The RR interval, QT interval(QT), corrected QT interval(QTc), QT dispersion and corrected QT dispersion(QTcD)were consecutively recorded using computerized measurement before and after administration of reversal agents in both groups.RR interval in the group N significantly decreased 1-4?min after reversal of the neuromuscular blockade, but not in the group S. However, in the groups N and S, QT interval, QTc interval, QTD and QTcD were not changed after reversal of the neuromuscular blockade. Moreover, there was no significant difference between both groups in QT interval, QTc interval, QTD and QTcD during the study.Our results suggest that neither neostigmine nor sugammadex may increase the risk of ventricular arrhythmia and cardiovascular events in reversal of the neuromuscular blockade under sevoflurane anesthesia

ロボット支援下前立腺全摘除術の麻酔管理：600例の経験から

ロボット支援下前立腺全摘除術（RARP）は恥骨後式前立腺全摘除術に比べ低侵襲で，当施設でも一般的な手術となり，既に700例近いRARPの麻酔管理を経験してきた．RARPを当施設で開始するにあたっては，泌尿器科医と手術室看護師，臨床工学士と共に，必要な情報収集と様々な準備を行い，幾度とシミュレーションを実施してきた結果，これまでに深刻な合併症を経験していない．しかしながら，RARPでは，良好な術野確保のため，高度な頭低位，気腹などの特殊な状況に患者が曝されるため，麻酔管理中は最新の注意を払う必要がある．RARPの安全性を確保するために，今後も経験を重ねて，RARPの麻酔管理の質を向上し行かなければならない．Robot associated radical prostatectomy（RARP）is less invasive than open radical retropubic prostatectomy. RARP has become popular in our facility. We have already experienced near 700 cases about anesthetic management of RARP. Before starting RARP in our facility, we have obtained many required knowledges, prepared many things and done its simulations together with urologists, nurses and clinical engineers. Fortunately, until now, we have never experienced serious problems during its peri-operative management. To obtain superior surgical field during RARP, there are many special situations, such as head-down tilt and pneumoperitoneum, to patients. So that, we should pay careful attention about anesthetic management of RARP and further improve anesthetic management of RARP to increase safety based on our experiences

Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors.

Peripheral inflammation initiates changes in spinal nociceptive processing leading to hyperalgesia. Previously, we demonstrated that among 102 lipid species detected by LC-MS/MS analysis in rat spinal cord, the most notable increases that occur after intraplantar carrageenan are metabolites of 12-lipoxygenases (12-LOX), particularly hepoxilins (HXA(3) and HXB(3)). Thus, we examined involvement of spinal LOX enzymes in inflammatory hyperalgesia. In the current work, we found that intrathecal (IT) delivery of the LOX inhibitor nordihydroguaiaretic acid prevented the carrageenan-evoked increase in spinal HXB(3) at doses that attenuated the associated hyperalgesia. Furthermore, IT delivery of inhibitors targeting 12-LOX (CDC, Baicalein), but not 5-LOX (Zileuton) dose-dependently attenuated tactile allodynia. Similarly, IT delivery of 12-LOX metabolites of arachidonic acid 12(S)-HpETE, 12(S)-HETE, HXA(3), or HXB(3) evoked profound, persistent tactile allodynia, but 12(S)-HpETE and HXA(3) produced relatively modest, transient heat hyperalgesia. The pronociceptive effect of HXA(3) correlated with enhanced release of Substance P from primary sensory afferents. Importantly, HXA(3) triggered sustained mobilization of calcium in cells stably overexpressing TRPV1 or TRPA1 receptors and in acutely dissociated rodent sensory neurons. Constitutive deletion or antagonists of TRPV1 (AMG9810) or TRPA1 (HC030031) attenuated this action. Furthermore, pretreatment with antihyperalgesic doses of AMG9810 or HC030031 reduced spinal HXA(3)-evoked allodynia. These data indicate that spinal HXA(3) is increased by peripheral inflammation and promotes initiation of facilitated nociceptive processing through direct activation of TRPV1 and TRPA1 at central terminals