Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons.

Remimazolam is an ultra-short benzodiazepine that acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain and induces sedation. Although GABA receptors are found localized in the spinal dorsal horn, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn. Behavioral measures, immunohistochemistry, and in vitro whole-cell patch-clamp recordings of dorsal horn neurons were used to assess synaptic transmission. Intrathecal injection of remimazolam induced behavioral analgesia in inflammatory pain-induced mechanical allodynia (six rats/dose; p < 0.05). Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation (five rats/group, p < 0.05). In vitro whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents, prolonged the decay time (six rats; p < 0.05), and enhanced GABA currents induced by exogenous GABA (seven rats; p < 0.01). However, remimazolam did not affect miniature excitatory post-synaptic currents or amplitude of monosynaptic excitatory post-synaptic currents evoked by Aδ- and C-fiber stimulation (seven rats; p > 0.05). This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn, suggesting its potential utility as a spinal analgesic for inflammatory pain.

Delayed paraparesis after posterior spinal fusion for congenital scoliosis: a case report.

INTRODUCTION: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis. CASE PRESENTATION: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits. DISCUSSION: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient.

Omega-conotoxin MVIIA reduces neuropathic pain after spinal cord injury by inhibiting N-type voltage-dependent calcium channels on spinal dorsal horn.

Spinal cord injury (SCI) leads to the development of neuropathic pain. Although a multitude of pathological processes contribute to SCI-induced pain, excessive intracellular calcium accumulation and voltage-gated calcium-channel upregulation play critical roles in SCI-induced pain. However, the role of calcium-channel blockers in SCI-induced pain is unknown. Omega-conotoxin MVIIA (MVIIA) is a calcium-channel blocker that selectively inhibits N-type voltage-dependent calcium channels and demonstrates neuroprotective effects. Therefore, we investigated spinal analgesic actions and cellular mechanisms underlying the analgesic effects of MVIIA in SCI. We used SCI-induced pain model rats and conducted behavioral tests, immunohistochemical analyses, and electrophysiological experiments (in vitro whole-cell patch-clamp recording and in vivo extracellular recording). A behavior study suggested intrathecal MVIIA administration in the acute phase after SCI induced analgesia for mechanical allodynia. Immunohistochemical experiments and in vivo extracellular recordings suggested that MVIIA induces analgesia in SCI-induced pain by directly inhibiting neuronal activity in the superficial spinal dorsal horn. In vitro whole-cell patch-clamp recording showed that MVIIA inhibits presynaptic N-type voltage-dependent calcium channels expressed on primary afferent Aδ-and C-fiber terminals and suppresses the presynaptic glutamate release from substantia gelatinosa in the spinal dorsal horn. In conclusion, MVIIA administration in the acute phase after SCI may induce analgesia in SCI-induced pain by inhibiting N-type voltage-dependent calcium channels on Aδ-and C-fiber terminals in the spinal dorsal horn, resulting in decreased neuronal excitability enhanced by SCI-induced pain.

Surfactant-Free Decellularization of Porcine Aortic Tissue by Subcritical Dimethyl Ether.

Porcine aortic tissue was decellularized by subcritical dimethyl ether (DME) used as an alternative to the surfactant sodium dodecyl sulfate. The process included three steps. For the first step, lipids were extracted from the porcine aorta using subcritical DME at 23 °C with a DME pressure of 0.56 MPa. Next, DME was evaporated from the aorta under atmospheric pressure and temperature. The second step involved DNA fragmentation by DNase, which was primarily identical to the common method. For the third step, similar to the common method, DNA fragments were removed by washing with water and ethanol. After 3 days of DNase treatment, the amount of DNA remaining in the porcine aorta was 40 ng/dry-mg, which was lower than the standard value of 50 ng/mg-dry. Hematoxylin and eosin staining showed that most cell nuclei were removed from the aorta. These results demonstrate that subcritical DME eliminates the need to utilize surfactants.

Ethanol-free antisolvent crystallization of glycine by liquefied dimethyl ether.

Liquefied dimethyl ether (DME) was employed as an antisolvent to crystallize glycine from its aqueous solution. The proposed method can be performed at 20-25 °C and has the potential to reduce the energy consumption of drying or crystallizing using ethanol. α-Glycine crystals were successfully obtained from glycine aqueous solutions by mixing in liquefied DME, which was easily removed from the crystals by decompression. Contact with a liquefied DME/water mixture and small γ-glycine crystals resulted in the α-glycine converting to γ-glycine. This was only observed for saturated glycine solutions. We speculated that this conversion occurs via a solution-mediated transition. Pure liquefied DME is not capable of promoting solvent-mediated transitions, so saturated glycine solutions treated with the pure antisolvent can give α-glycine as the sole product.

Lipid emulsion injection-induced reversal of cardiac toxicity and acceleration of emergence from general anesthesia after scalp infiltration of a local anesthetic: a case report.

BACKGROUND: A scalp block or wound infiltration of local anesthetic is thought to effectively control post-craniotomy pain. However, it can result in local anesthetic toxicity (LAST), which is difficult to distinguish from brain damage due to the surgical procedure when emergence from general anesthesia is delayed. Lipid rescue (infusion of a lipid emulsion) is a widely accepted treatment for LAST. CASE PRESENTATION: A 64-year-old man underwent surgical resection of a glioma in the brainstem. While still under general anesthesia, and before suturing of the wound, he received a 20-mL scalp infusion of ropivacaine 0.75%. His emergence from anesthesia was delayed, his respiration was suppressed, and premature ventricular contractions occurred; all of which are symptoms of LAST. Injection of a 20% lipid emulsion rapidly alleviated these symptoms. Interestingly, the blood concentration of ropivacaine increased after lipid rescue. CONCLUSIONS: The increase in ropivacaine concentration in the blood after lipid rescue suggests that the intravenously administered lipid emulsion absorbed the ropivacaine from the intoxicated brain and heart tissue. This finding is consistent with the lipid sink theory as a mechanistic explanation of lipid rescue.