痛覚、痒み、及びその障害 Pain, Itch and Their Disorders
P2-2-131 遅発性筋痛を生じる筋伸張パラメータ Stretching parameters leading to delayed onset muscle soreness in rats ○林功栄1, 阿部真博2, 水村和枝3, 山中章弘1, 田口徹1 ○Koei Hayashi1, Masahiro Abe2, Kazue Mizumura3, Akihiro Yamanaka1, Toru Taguchi1 名古屋大・環医研・神経II1, ビタカイン製薬（株）学術部2, 中部大・生命健康科学・理学療法3 Dept. Neurosci. II, Res. Inst. Environ. Med., Nagoya Univ., Nagoya, Japan.1, Med. Inform. Dept., Vitacain Pharmaceutical Co. Ltd., Osaka, Japan.2, Coll. Life Health Sci., Chubu Univ., Kasugai, Japan.3 Strenuous exercise with lengthening contraction (LC) causes tenderness and movement-related pain with some delay (delayed onset muscle soreness, DOMS). To know stretching parameters that elicit DOMS is important for its prevention because the pain severely restricts one's physical activities in daily living. The aim of the present study was to examine which range of motion (ROM) and angular velocity of the muscle stretch during LC lead to DOMS. Under inhalation anesthesia with 1.5% isoflurane, ankle extensor muscles of rats were given repetitive LC with a customized device (NDH-1, Bio Research Center) which precisely controls parameters of stretching. The effect of various ROM (30º, 60º, 90º, and 120º at the constant angular velocity of 200º/s) and angular velocity (50º/s, 100º/s, 200º/s, and 400º/s at the ROM of 90º) was tested while the number of LC was fixed at 50 times. Mechanical hyperalgesia (tenderness) was quantified by measuring the mechanical withdrawal threshold of the exercised muscle before, 3 hours, 1, 2, 3, 4, and 5 days after LC. Here we found that LC at the ROM of 60º, 90º, and 120º significantly decreased the withdrawal threshold in a ROM-dependent manner while that at 30º did not, and that the stretching parameters at the angular velocities of 100º/s, 200º/s, and 400º/s significantly decreased the threshold in an angular velocity-dependent manner while that at 50º/s did not. Repetitive stretching of the muscle alone without muscle contraction had no effect on the nociceptive threshold at all ROM and angular velocities tested. These results suggest that the ROM and the angular velocity of the muscle stretch during LC were important determinants leading to DOMS.	P2-2-132 三叉神経感覚系におけるガストリン放出ペプチドの分布 Distribution of gastrin-releasing peptide in the trigeminal sensory system ○高浪景子1, 坂本浩隆2, 松田賢一1, 佐藤慧太2, 井上海平1,3, 山田俊児1, 谷田任司1, 越智拓海2, 坂本竜哉2, 河田光博1 ○Keiko Takanami1, Hirotaka Sakamoto2, Ken-Ichi Matsuda1, Keita Satoh2, Kaihei Inoue1,3, Shunji Yamada1, Takashi Tanida1, Takumi Ochi2, Tatsuya Sakamoto2, Mitsuhiro Kawata1 京都府医大院・解剖学・生体構造科学1, 岡山大院・自然科学研究科・理学部附属臨海実験所2, 関西健康科学専門学校3 Dept Anatomy and Neurobiology, Kyoto Prefectural Unv of Medicine, Kyoto1, Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama Unv, Okayama2, Kansai College of Health Sciences, Hyogo3 Gastrin-releasing peptide (GRP) is widely distributed in the central nervous system, and related to the regulation of many physiological functions. Recently, it is reported that GRP is also expressed in the dorsal root ganglion and spinal cord, and participates in the regulation of itch sensation in the spinal level. But, there are no reports of GRP expression in the trigeminal sensory system. In this study, we investigated the localization of GRP in the rat trigeminal sensory system using immunohistochemistry. In the trigeminal ganglion, GRP-immunoreactivity (ir) was mainly observed in the cell bodies and fibers of the small-sized neurons. GRP-ir neurons showed the coexpression with other peptides, such as CGRP and substance P, but not with isolectin B4, nonpeptidergic neuronal marker. We examined the expression of GRP in the brainstem trigeminal sensory nuclei. We found a dense accumulation of GRP-ir fibers in the superficial layer of caudal part of spinal trigeminal nucleus (STN). In contrast, GRP-ir was sparse in the interpolar part and oral part of STN and principal sensory trigeminal nucleus. In the caudal part of STN, GRP-ir fibers showed the coexpression with the CGRP and substance P. These results suggested that GRP may play an important role in the integration of the information of itch sensation in the trigeminal sensory system as well as the spinal somatosensory system.
P2-2-133 エストロゲンは代謝型グルタミン酸受容体を介し三叉神経脊髄路核尾側亜核における侵害受容ニューロンの興奮性を変調させる Estrogen acts through mGluR1 to modulate TMJ-evoked activity of trigeminal subnucleus caudalis neurons in female rats ○田代晃正1, 田村吏沙1, 西田育弘1 ○Akimasa Tashiro1, Risa Tamura1, Yasuhiro Nishida1 防衛医科大学校生理学教室1 Dept. Physiol. Nat.Def.Med. Coll. Saitama . Japan1 Sex hormone status is a risk factor in painful temporomandibular disorders (TMD). Previously we reported that estrogen (E2) enhanced nociceptive processing of TMJ input by laminae I-II, but not lamina V units. The mechanisms for this enhancement are not known. To determine if estrogen interacts with metabotropic glutamate receptor1 (mGluR1) to modulate nociceptive input from the TMJ region, single units were recorded in laminae I-II at the spinomedullary (Vc/C2) junction from ovariectomied female rats (OvX) treated with high E2 (40μg/d, HE2), low E2 (4μg/d, LE2) and male rats. Under isoflurane anesthesia TMJ units were activated by ATP (1 mM, 20μl) injected into the joint space. The mGluR1 antagonist, CPCCOEt (50-500μM) was applied topically to Vc/C2 surface 10 min before test injections of ATP. ATP-evoked responses of TMJ units in HE2 were enhanced versus LE2 (p< 0.05). The low dose of CPCCOEt (50μM) caused a near maximal inhibition of ATP-evoked activity of units from HE2 (P<0.01), but not effect on units from LE2. Topical high dose of CPCCOEt (500μM) affected ATP-evoked responses in both groups. mGluR1 inhibition had only minor effects on spontaneous unit activity of TMJ units in both groups. These suggested that mGluR1 activation contributed to the E2-mediated enhanced response in HE2 rats. It is concluded that estrogen acts in part through mGluR1 dependent mechanism to enhance TMJ nociceptive processing by laminae I-II neurons in the medullary dorsal horn.	P2-2-134 セリンラセマーゼノックアウトマウスでの炎症性疼痛感受性の上昇 Increased sensitivity to inflammatory pain induced by subcutenous formalin injection in serine racemase knock-out mice ○田端彩子1, 森寿1, 井上蘭1 ○Ayako Tabata-Imai1, Hisashi Mori1, Ran Inoue1 富山大院・医・分子神経科学1 Dept Mol Neurosci, Univ of Toyama, Toyama1 D-serine, an endogenous co-agonist for the glycine-binding site of N-methyl-D-aspartate receptor (NMDAR), is widely distributed in central nervous system and synthesized from L-serine by serine racemase (SR). The NMDAR plays an important role in pain transduction including the central sensitization that eventually causes hyperalgesia. However, the role of D-serine in pain transduction is unknown at present. To evaluate the involvement of D-serine in pain transduction, we conducted the formalin test, an acute inflammatory pain model, using SR knock-out (KO) mice. Formalin injected subcutenously into the left hind paw induced bi-phasic pain response of licking on the injected paw in SR-KO and wild-type (WT) mice. The duration of licking behavior was significantly prolonged in SR-KO mice during the second phase of the formalin test. Immunofluorescence staining revealed that the formalin injection into the left hind paw induced c-Fos and phosphorylated extracellular signal regulated kinase (p-ERK) proteins in neurons at the superficial layers of ipsilateral dorsal horn (DH) of the spinal cord in WT and SR-KO mice. The number of the c-Fos and p-ERK positive cells in the lamina I-II of the DH was significantly increased in SR-KO mice. Furthermore, SR in WT mice was mainly distributed in the lamina II of the DH. These findings demonstrate that SR-KO mice showed increased sensitivity to inflammatory pain suggesting an important role of D-serine in pain transduction
P2-2-135 敗血症性脳症における感覚機能異常の分子機構解明に向けた研究 Possible involvement of NR2B subunit in septic encephalopathy ○吉川直1, 今村行雄2, 村上由希2, 三谷智子2, 松本直也3, 小倉裕司3, 嶋津岳士3, 精山明敏1 ○Nao Yoshikawa1, Yukio Imamura2, Yuki Murakami2, Satoko Mitani2, Naoya Matsumoto3, Hiroshi Ogura3, Takeshi Shimazu3, Akitoshi Seiyama1 京都大学医学部人間健康科学科　検査技術科学専攻　情報理工医療学講座1, 京都大学工学研究科・医学研究科　安寧の都市ユニット2, 大阪大学医学部附属病院　高度救命救急センター3 Human Health Science, Kyoto University Medical School, Kyoto1, Unit for Liveable Cities, Kyoto University Graduate School Engineering and Medicine2, Dept. Trauma and Acute Critical Care Center, Osaka Univ. Hspital3 Sepsis is a devastating medical condition characterized by systematic inflammatory response syndrome (SIRS). It has been suggested that sepsis results in multiple-organ dysfunction syndrome in response to the processes: 1) endotoxemia (i.e., drastic increase of endotoxin in the blood), 2) SIRS and 3) septic encephalopathy (SE). SE patients show mental confusion, sensory neuronal impairment and long-term cognitive impairment. Patho-physiological mechanisms of brain dysfunction caused by sepsis provoke the development of medical intervention against SE. In sensory neuronal impairment, degeneration of N-methyl-D-aspartate receptors (NMDARs) and secretion of interleukin-1β (IL-1β ) may be involved. NMDARs contain two NR1 subunits paired with two NR2 subunits. NMDARs containing the NR2B subunits localized in thalamus implicate in neuronal death in encephalitis/encephalopathy. On the other hand, IL-1β specifically binds to interleukin-1 receptors (IL-1Rs) on neuronal cell membrane and induces synaptic plasticity deficiency. To examine a possible role of NR2B and IL-1 in SE, we examined the alteration of distribution and expression of NR2B and IL-1R in septic encephalopathy with immunohistochemical staining. At first, the numbers of IL-1R- and NR2B-positive cells in the whole brain were increased at 20 h after intraperitoneal injection of lipopolysaccharide (LPS) (1mg/kg) in mice. Second, a part of NR2B was overlapped with IL-1R. These findings suggest that NR2B increased in septic encephalopathy may be associated with IL-1R. The molecular mechanisms involved are currently under investigation and these new data will be also presented at the meeting.	P2-2-136 痛みに伴った脊髄後角でのリン酸化ERKと神経可塑性への亜鉛の関与 Contribution of zinc to the pain-induced ERK phosphorylation and neuronal plasticity in the spinal dorsal horn ○岩佐光毅1, 村瀬一之1,2, 池田弘1,2 ○Kouki Iwasa1, Kazuyuki Murase1,2, Hiroshi Ikeda1,2 福井大院・工・知能システム1, 福井大学 生命科学複合研究育成センター2 Dept. of Human and Artificial Intelligence Systems, Grad. Sch. of Engineering, Univ. of Fukui1, Res. and Education Program for Life Sci., Univ. of Fukui2 Zinc is abundant in the central nervous system including the spinal dorsal horn and regulates pain. Recently, the contribution of zinc to synaptic plasticity is also reported. In this study, we examined the contribution of zinc to the phosphorylation expressions of extracellular signal-regulated kinase (p-ERK) induced by the inflammatory pain and to the neuronal plasticity of optically-recorded neuronal excitation in the mouse spinal dorsal horn. Intracellular zinc detected by Timm's stain was significantly decreased in the spinal dorsal horn 6 h after intraperitoneal injection of the zinc chelator, clioquinol (CQ, 100 mg/kg). The sensitivity of pain induced by formalin injection into a side of hind paw was increased in the CQ injected mice. The expression of p-ERK in the lamina I-II of spinal dorsal horn induced by formalin injection was increased in CQ injected mice. In the superficial layer of spinal dorsal horn, the plastic change of optically-recorded neuronal excitation triggered by the low-frequency conditioning stimulation to the dorsal root was affected by chelation of zinc with CQ.
P2-2-137 痛みによる情動と痛覚過敏に対する前帯状回のERKとNMDA受容体の関与 Involvement of Extracellular Signal-Regulated Kinase and NMDA receptor in the Anterior Cingulate Cortex in the affective component and hypersensitivity of pain ○林努1, 村瀬一之1,2, 池田弘1,2 ○Tsutomu Hayashi1, Kazuyuki Musase1,2, Hiroshi Ikeda1,2 福井大院・工・知能システム1, 福井大学 生命科学複合研究育成センター2 Dept. of Human and Artificial Intelligence Systems, Grad. Sch. of Engineering, Univ. of Fukui1, Res. and Education Program for Life Sci., Univ. of Fukui2 The anterior cingulate cortex (ACC) has been implicated as a key structure in the affective component of pain. However, the detailed mechanisms are not clear. In this study, we examined the role of extracellular signal-regulated kinase (ERK) activation and NMDA receptor on the affection and the sensitivity to pain induced by formalin injection into a side of hindpaw of mice. By immunohistochemical staining of phosphorylation of ERK (p-ERK), the expression of p-ERK in the rostral ACC (rACC) was increased by the formalin injection. Bilateral microinjections of ERK inhibitor PD98059 (50nmol) and NMDA receptor antagonist D-AP5 (50nmol) in the rACC through the guide cannula prevented the increase of p-ERK expression in the rACC induced by the formalin injection and such increase of anxiety-related behavior was inhibited by bilateral microinjections of PD98059 and D-AP5 in the rACC. Pain behavior induced by formalin injection was decreased by injection of D-AP5, but not by injection of PD98059 in rACC. These results suggest that ERK activation via NMDA receptor in the rACC is contribute to the affective component of pain, and activation of any additional intracellular mechanisms via the NMDA receptor may be contribute to the hypersensitivity of pain.	P2-2-138 皮膚温度感覚についての知覚学習 Perceptual learning of cutaneous thermal sensation ○眞野博彰1, 吉田和子2, 柴田和久2,3, 張素怡1, コルツェンバァグマァティン4, レンギェルメイト5, 川人光男2, シィモアベン1,5 ○Hiroaki Mano1, Wako Yoshida2, Kazuhisa Shibata2,3, Suyi Zhang1, Martin Koltzenburg4, Mate Lengyel5, Mitsuo Kawato2, Ben Seymour1,5 独立行政法人 情報通信研究機構　脳情報通信融合研究センター 脳情報通信融合研究室1, 国際電気通信基礎技術研究所2, ブラウン大学3, ロンドン大学ユニバーシティ・カレッジ4, ケンブリッジ大学5 CiNet, NICT, Osaka, Japan1, Advanced Telecommunications Research Institute International (ATR), Kyoto, Japan.2, Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, Rhode Island, USA.3, Institute of Neurology, UCL, London, UK.4, Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Cambridge, UK.5 Human sensation can be divided into exteroception - the ability to sense one's external environment, and interoception - the ability to sense the physiological condition of our internal bodily environment. Interoception incorporates the sensory modalities of temperature and pain, the afferent pathways of which are anatomically and physiologically distinct from exteroceptive somato-sensation, being peripherally transmitted by small myelinated and unmyelinated fibres and to the brain via the spinothalamic tract. The central (cortical) representation of temperature and pain is controversial, and one major missing component of previous studies is the lack of any demonstration of perceptual learning - the hallmark of cortical processing. Here, we present preliminary data from a temperature discrimination task, in which healthy participants were required to identify very small changes in warmth and cooling of a temperature thermode attached to the leg. We used a 1-interval detection paradigm in which subjects were required to detect the presence or absence of very small pulses of temperature: either decreases from a cool baseline (25C, which selectively activates cold fibers) or increases from a warm baseline (39C, which selectively activates warm fibers), at a range of difficulties on the right or left leg. We then extensively trained subjects on one specific condition: either warmth or cooling, on either right or left, over 1 week. Subjects were then re-tested to assess whether their detection ability improved as a function of training. We present behavioural data that suggests preliminary evidence that thermal perceptual learning is possible, and address the question of specificity for temperature and laterality.
P2-2-139 TRPM2の遺伝子欠損による各種疼痛モデルにおける痛み抑制 TRPM2 deficiency attenuates various types of pain ○朝倉佳代子1, 宗可奈子1, 原口佳代1, 勇昂一1, 崎元伸哉1, 白川久志1, 中川貴之1, 金子周司1 ○Kayoko Asakura1, Kanako So1, Kayo Haraguchi1, Kouichi Isami1, Shinya Sakimoto1, Hisashi Shirakawa1, Takayuki Nakagawa1, Shuji Kaneko1 京都大学大学院薬学研究科　生体機能解析学分野1 Dept. Mol. Pharmacol., Grad. Sch. Pharm. Sci., Kyoto Univ.1 TRPM2 acts as a sensor for reactive oxygen species, and is abundantly expressed in immune cells including macrophage, neutrophil, and microglia. Recently, we reported that TRPM2 expressed in macrophages and spinal microglia contributes to pathological pain by aggravating pronociceptive inflammatory responses (J Neurosci, 2012). In the previous report, TRPM2 deficiency showed inhibitory effects in the intraperitoneal acetic acid-induced writhing test, the carrageenan-induced inflammatory pain model and peripheral nerve injury (partial sciatic nerve ligation and spinal nerve transaction)-induced neuropathic pain models in mice. In this study, we further examined the effect of TRPM2 deficiency on various kinds of pain models. In formalin test, TRPM2-KO mice showed normal nocifensive behaviors in the first phase, while they were significantly reduced in the second phase. In carrageenan-induced inflammatory pain model, mechanical allodynia and thermal hyperalgesia were attenuated in TRPM2-KO mice, whereas no difference was observed in Complete Freund's adjuvant-induced inflammatory pain model. Mechanical allodynia in diabetic neuropathy model induced by streptozotocin (75 mg/kg, i.v.) was significantly attenuated in TRPM2-KO mice without affecting blood glucose level after an oral glucose load. Mechanical allodynia in peripheral neuropathy model induced by a chemotherapeutic drug, paclitaxel (4 mg/kg × 4, i.p.), was significantly attenuated in TRPM2-KO mice. In experimental autoimmune encephalomyelitis (EAE) model with MOG peptide, both EAE score and mechanical allodynia were significantly attenuated in TRPM2-KO mice. Finally, the mechanical allodynia evoked by intraplantar injection of LPS-stimulated cultured macrophages or neutrophils derived from TRPM2-KO were significantly weaker than WT macrophages or neutrophils. Taken together, these results suggest that TRPM2 plays important roles in the pathogenesis of various types of pathological pain.	P2-2-140 脊髄ミクログリアに発現する転写因子Mafbの神経障害性疼痛発症への関与 Transcription factor MafB mediates activation process of spinal microglia that contributes to neuropathic pain development ○齊藤秀俊1, 増田潤哉1, 増田隆博1, 津田誠1, 井上和秀1 ○Hidetoshi Saitoh1, Junya Masuda1, Takahiro Masuda1, Makoto Tsuda1, Kazuhide Inoue1 九州大学大学院　薬学研究院　薬理学分野1 Dept Mol. Sys. Pharmacol., Grad. Sch. Pharmaceu. Sci., Kyushu University, Fukuoka1 Spinal microglia immediately transform into activated phenotype following peripheral nerve injury, which is a key event for development of neuropathic pain. However, the underlying mechanism of their functional shift from resting to hyperactive type remains unknown. Here we found MafB, a known pivotal transcriptional regulator of macrophage differentiation, involved in the transformation of microglia in the mouse model of neuropathic pain. Peripheral nerve transection caused a marked increase of MafB expression exclusively in the nuclei of a subset of spinal microglia. The MafB positive microglia appeared early after nerve injury and displayed activation phenotype represented by a proliferation marker and activated phenotype marker CD68. In the cultured microglia, MafB knockdown by specific siRNA reduced the expression level of pain-related genes. Intrathecal delivery of siRNA successfully suppressed the injury-induced MafB upregulation and alleviated development of allodynia, a typical symptom of neuropathic pain. CCL21, an important player in the onset of neuropathic pain derived from injured neurons, enhanced microglialMafB expression both in vitro and in vivo. Taken together, we propose that MafB is a key mediator in the peripheral nerve injury-induced phenotypic alteration of spinal microglia which contributes to development of neuropathic pain.
P2-2-141 痒み求心性入力を受けるラット脊髄後角細胞のin vivo発火パターン解析 Firing pattern of spinal dorsal horn neurons receiving pruritogen serotonin-responsive afferents in the rat spinal cord ○歌大介1, 安東嗣修2, 倉石泰2, 井本敬二1,3, 古江秀昌1,3 ○Daisuke Uta1, Tsugunobu Ando2, Yasushi Kuraishi2, Keiji Imoto1,3, Hidemasa Furue1,3 生理研・生体情報・神経シグナル1, 富山大・医薬・応用薬理2, 総研大・生理科学3 Div. Neural Signaling, Dept. Info. physiol, Natl. Inst. Physiol. Sci., Okazaki, Japan1, Dept. Applied Pharm, Grad. Sch. Med. and Pharm. Sci., Univ. Toyama, Toyama, Japan2, Dept. Physiol. Sci., SOKENDAI, Okazaki, Japan3 Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin. We have previously shown that pruritic synaptic responses evoked in spinal dorsal horn (SDH) neurons of adult rats by using an in vivo whole-cell patch-clamp recording technique. Under voltage-clamp conditions, topically application of serotonin to the skin increased the frequency of the large amplitudes of spontaneous EPSCs in about 30 % of the neurons recorded. In this study, we examined the firing patterns of the SDH neurons receiving serotonin-responsive afferent fibers. In current-clamp mode, SDH neurons discharged action potentials in response to a just supra-threshold current pulse. SG neurons tested were classified into five types: delayed firing, sustained repetitive firing, phasic firing, initial firing and other firing (e.g. single). Many (70%) of the serotonin-responsive SDH neurons were the delayed and sustained repetitive firing types, although serotonin-unresponsive neurons were also found in these two types of SDH neurons. In the initial firing type, serotonin-responsive neurons were slightly-detected. A previous study explored the relationship between the morphological class of SDH neurons and their firing pattern, has shown that vertical cells exhibit the delayed or sustained firing type, and radial cells exhibit the phasic firing type. Moreover, central cells are reported to exhibit the initial firing pattern of discharge. In combination with previous studies, the present results suggest that activation of serotonin-responsive neurons facilitates spontaneous excitatory synaptic transmission from primary afferents onto mainly delayed firing and sustained repetitive firing type neurons which are morphologically classified vertical and radial cells.	P2-2-142 痛みの選択的抑制とTTX抵抗性Naチャネルに対するレボブピバカインのuse-dependentブロック Selective use-dependent inhibition of levobupivacaine on TTX resistant (NaV1.8) sodium currents ○川津領一1,2, 井本敬二1,3, 歌大介1, 岡本孝史2, 田矢廣司2, 山村陸朗2, 池田雅弘2, 古江秀昌1,3 ○Ryoichi Kawatsu1,2, Keiji Imoto1,3, Daisuke Uta1, Takashi Okamoto2, Koji Taya2, Yoshiro Yamamura2, Masahiro Ikeda2, Hidemasa Furue1,3 生理研・神経シグナル1, 丸石製薬・中央研究所2, 総研大・生命科学3 Dept Information Physiol, NIPS1, Cen Res Lab, Maruishi Pharm Co Ltd, Osaka2, Sch Life Sci, Grad Univ Adv Study3 Levobupivacaine (popscaine®), S-isomer of bupivacaine, is clinically used as a local anesthetic and less cardiotoxic than racemic bupivacaine. Our previous studies have shown that levobupivacaine selectively inhibited action potentials elicited in noxious C and Aδ fibers. Little is known, however, which kinds of Na channels are preferentially suppressed by levobupivacaine. In this study, we examined inhibitory action of levobupivacaine on TTX resistant NaV1.8 sodium channel and compared the inhibitory action of levobupivacaine with those of other local anesthetics. NaV1.8 channel was expressed in a dosal root ganglion-derived cell line, ND7/23. In the presence of TTX, depolarizing voltage-clamp pulses elicited an inward current and the voltage-current relationship was identical to those for NaV1.8 sodium channel shown in previous studies. Levobupivacaine, ropibacaine, bupivacaine and lidocaine all inhibited the Nav1.8 sodium current with IC50s of 178, 260, 140 and 318 μM, respectively. Levobupibacaine had a more potent use-dependent block of NaV1.8 sodium currents in comparison with other local anesthetics. The present and our previous results suggest that S-isomer of local anesthetics, especially levobupivacaine, selectively inhibit persistent noxious information by conduction block in C and δ fibers expressing NaV1.8 channel.

上部に戻る

前に戻る