Yoshikazu Matsuoka

Decoy strategy targeting the brain-derived neurotrophic factor exon I to attenuate tactile allodynia in the neuropathic pain model of rats.

The mechanism underlying neuropathic pain is still largely unclear. Recently, much attention has been focused on the role of brain-derived neurotrophic factor (BDNF) as a neuromodulator in the spinal cord. We previously reported that the expression of Bdnf exon I mRNA was remarkably up-regulated in the dorsal root ganglion (DRG) neurons with the rat L5 spinal nerve ligation (SNL) model. In the present study, we investigated whether neuropathic pain response would be reduced by the inhibition of the Bdnf exon I in the rat SNL model. We identified the promoter region of exon I and synthesized the decoy ODNs targeting the region. Reverse transcription-polymerase chain reaction analysis confirmed that the decoy ODN treatment reduced SNL-induced Bdnf exon I mRNA up-regulation in ipsilateral L4 and L5 DRGs. Furthermore, post-treatment with the decoy ODNs significantly attenuated SNL-induced tactile allodynia. This study suggested that decoy ODNs targeting the Bdnf exon I might provide a novel analgesic strategy for the treatment of neuropathic pain.

Altered response to formalin by L5 spinal nerve ligation in rats: a behavioral and molecular study.

BACKGROUND:The status of neuropathic pain alters the responsiveness to formalin injection in rats. However, the mechanism by which this alteration occurs is unknown. METHODS:We used immunocytochemistry to examine the expression of brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the spinal cord of rats with L5 spinal nerve ligation (SNL)-induced neuropathy, and investigated the expression of c-Fos in the spinal cord after injection of formalin in the hindpaw of rats with SNL. RESULTS:Four weeks after SNL, the withdrawal threshold was significantly lower in the SNL group than in the sham-operated (sham) group (n = 12 per group, P < 0.05). In the SNL group, expression of BDNF in the L4 (P < 0.05) and L5 (P < 0.01) superficial dorsal horn was significantly decreased compared to that in the sham group. CGRP protein in the L5 but not in the L4, dorsal horn was significantly decreased compared to that in the sham group (P < 0.01). After formalin injection, spontaneous pain responses in the SNL group were significantly decreased compared to those in the sham group (P < 0.05). Immunolabeling for c-Fos was significantly decreased in the L4 and L5 dorsal horn in the SNL group (P < 0.01). CONCLUSION:Our examination of c-Fos distribution indicates that decreased neuronal activity in the spinal cord in response to inflammatory pain may be important for altering the perception of acute pain. Decreased BDNF expression in response to SNL-induced neuropathy may be involved in this alteration.

Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model

Metastatic bone cancer causes severe pain, but current treatments often provide insufficient pain relief. One of the reasons is that mechanisms underlying bone cancer pain are not solved completely. Our previous studies have shown that brain-derived neurotrophic factor (BDNF), known as a member of the neurotrophic family, is an important molecule in the pathological pain state in some pain models. We hypothesized that expression changes of BDNF may be one of the factors related to bone cancer pain; in this study, we investigated changes of BDNF expression in dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA (messenger ribonucleic acid) and protein were significantly increased in L3 dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer cells. Among the eleven splice-variants of BDNF mRNA, exon 1–9 variant increased predominantly. Interestingly, the up-regulation of BDNF is localized in small neurons (mostly nociceptive neurons) but not in medium or large neurons (non-nociceptive neurons). Further, expression of nerve growth factor (NGF), which is known as a specific promoter of BDNF exon 1–9 variant, was significantly increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain.

Spinal nerve injury causes upregulation of ErbB2 and ErbB3 receptors in rat dorsal root ganglia

It is generally known that peripheral nerve injury causes changes in expression of some growth factors in the dorsal root ganglion. Altered expression of ErbB receptors, a well-known growth factor in somatic cells, reportedly follows peripheral nerve injury in the spinal dorsal horn; however, it remains unknown whether the expression of these receptors is altered in the dorsal root ganglion after nerve injury. Therefore, this study examined the gene expression profiles of ErbB receptors in bilateral lumbar (L)4/L5 dorsal root ganglia, using L5-selective spinal nerve ligation in model rats as a peripheral nerve injury model. The expression of ErbB2 and ErbB3 was observed in the dorsal root ganglia of the mature rat, despite ErbB1 and ErbB4 showing only subtle expression. We also demonstrated that peripheral nerve injury induced significant increases in ErbB2 and ErbB3 in the ipsilateral dorsal root ganglion as compared with uninjured nerve. Expression changes in ErbB receptors appear to play important roles in nerve injury and subsequent nerve regeneration.

A Case of Cardiac Arrest Due to Coronary Vasospasm on Extubation Following Thymectomy

大動脈弁閉鎖不全,僧帽弁閉鎖不全,三尖弁閉鎖不 全を認めた.冠動脈造影CTでは有意狭窄や石灰化 を認めなかった. 術式は仰臥位で胸骨正中切開下に拡大胸腺摘出術 が予定された.手術室入室時のバイタルサインは心 拍数(HR)68回/分,血圧(BP)138/84mmHg,SpO2 96%であった.腫瘍の脈管浸潤の可能性が高く遠心 ポンプ使用を念頭に置き,硬膜外麻酔は併用しなか った.全身麻酔はレミフェンタニル,プロポフォー ル,ロクロニウムで導入し,35Fr左気管支用ダブル ルーメンチューブを挿管した.導入後に左橈骨動脈 と右足背動脈に観血的動脈圧ラインを確保し,右大 腿静脈に中心静脈カテーテルを留置した.経食道心 エコー(transesophageal echocardiography:TEE) では,術前所見以外に異常はなかった.麻酔維持は プロポフォールTCI (target controlled infusion)設 定2μg/mLとレミフェンタニル0.1~0.3μg/kg/分 はじめに

Perioperative management center (Perio) for neurosurgical patients

Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7–14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 ± 0.3 days), compared to that in the non-PERIO group (4.7 ± 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff.

The inhibitory effect of locally injected dexmedetomidine on carrageenan-induced nociception in rats

Recent studies showed that the administration of dexmedetomidine relieved hyperalgesia in the presence of neuropathic pain. These findings have led to the hypothesis that the local administration of dexmedetomidine is useful for relieving acute inflammatory nociception, such as postoperative pain. Thus, we evaluated the inhibitory effect of locally injected dexmedetomidine on acute inflammatory nociception. Acute inflammatory nociception was induced by an intraplantar injection of 1% carrageenan into the hindpaws of rats, and dexmedetomidine was also injected combined with carrageenan. The paw withdrawal threshold based on von Frey filament stimulation was measured until 12 h after injection. We compared the area under the time-curve (AUC) between carrageenan and carrageenan with dexmedetomidine. To clarify that the action of dexmedetomidine was via α2-adrenoceptors, we evaluated the effect of yohimbine, a selective antagonist of α2-adrenoceptors, on the anti-nociception of dexmedetomidine. As the results, the intraplantar injection of carrageenan with over 10 μM dexmedetomidine significantly increased AUC, compared to that with only carrageenan injection. This effect of dexmedetomidine was reversed by the addition of yohimbine to carrageenan and dexmedetomidine. These results demonstrated that the locally injected dexmedetomidine was effective against carrageenan-induced inflammatory nociception via α2-adrenoceptors. The findings suggest that the local injection of dexmedetomidine is useful for relieving local acute inflammatory nociception.