The authors acknowledge the work that was done by the first author of the IoN-CCI model, Bart Vos&#8224;.

倫理の声明：動物が治療と研究IASP 11の倫理問題のための委員会のガイドラインに従って世話しています。プロトコルは、機関倫理委員会によって承認されています。 1.被験者<ol><li>雄のSprague-Dawleyラット（到着時250〜300グラム）を使用します。 </li><li> 40〜60％の湿度のコロニールーム、21±1℃の室温で固体底のケージでハウスラット。 </li><li>自由で水や食料を利用できるようにします。 </li><li> （20時間に点灯）逆12：12時間の明/暗サイクルの下でラットをしてください。 </li></ol> 2.手術<ol><li>ラット当たり、長い約6センチクロム腸結紮（5-0）を2枚準備し、乾燥し、堅くて脆くなるのを避けるために滅菌生理食塩水に配置します。 </li><li>ペントバルビタール（60mg / kg、腹腔内）で動物を麻酔し、アトロピン（0.1ミリグラム/ kg、腹腔内）で処理します。片足とpinchiを拡張することによって、麻酔のレベルを監視適切な圧力が適用されていることを確認するために指の爪と指の間の皮膚のウェブngの。動物がその手足を曲げていないことを確認してください。必要に応じて、追加のペントバルビタールを投与します。 </li><li>正中線の頭皮切開を眼の中心に等距離の前後で約25mmで作製することができるように、ラットの頭部を剃ります。 </li><li>定位フレームにラットの頭を修正するか、またはそうでなければ、ラットの頭を固定。体温を維持するために加熱されたパッドの上にラットを置きます。 </li><li>乾燥による損傷を防ぐために、両眼に眼軟膏を適用します。 </li><li>その後ベータダイン、アルコールで剃ったエリアをスクラブ。 </li><li>頭蓋骨と鼻骨を露出し、ミッドライン頭皮の切開を行います。 </li><li> 2.16にステップ2.9を実行するために手術用顕微鏡を使用してください。 </li><li>綿棒とデュモン鉗子のペアを使用して、上顎、前頭、涙と頬骨骨によって形成された無料の軌道のエッジを解剖。そうに綿棒を使用してください可能な出血から血をのk。 </li><li>イオンへのアクセス権を与えるには、静かにイオンに優れ横切る前篩骨神経を引き伸ばし過ぎないように注意しながら、精密綿棒で眼窩内容をそらします。精密綿棒や拡散の動きを使用して、デュモン鉗子のペアを使用して、周囲の結合組織から遊離イ​​オンを分析。可能な出血から血液を吸収するために綿棒を使用してください。 </li><li>連結を実行するには、下向きの前頭骨に沿ってクロム腸の単一片の一方の端を押して、イオンに内側およびイオンに数ミリが平行と劣る進めます。リガチャーは、現在イオンと前頭骨との間の所定の位置に保持されています。 </li><li>合字の近くにそれを置くために、イオンの下に45度傾斜したデュモン鉗子の先端をスリップ。静かに鉗子の結紮先端を明らかにするために、横方向にイオンを撤回。グリップピンセットで結紮イオンの下から横方向に鉗子を撤回。 </LI&gt; <li>合字の両端が多かれ少なかれ等距離イオンからなるまで、眼窩から合字を引き出します。 </li><li>合字の両端から「スリップノット」は狭窄度にわたって完全な制御を可能にし、イオンに対して結び目をスライドするようにしてください。神経の直径はちょうど顕著な量だけ減少されるように、イオンを収縮するために、さらに結び目をスライドさせます。くびれの量が一定になるように（ すなわち、滑りからスリット結び目を防ぐために）、スリップノットの上に通常の結び目を作ります。 </li><li>結び目から自由端の約2mmを残して合字をカットします。 </li><li> 2ミリメートル離れて、最初から二番目の連結を行うこと（2.15に対して2.11ステップ）と同じ手順を繰り返します。 </li><li>偽手術の場合は、ステップ2.2 2.10を実行します。 </li><li>ポリエステル縫合糸（4-0）を使用して頭皮の切開を閉じ、ラットを加熱パッド上で回復することができます。それは十分な短所を取り戻したまで無人の動物を放置しないでくださいciousness胸骨横臥位を維持し、それが完全に回復するまで、他の動物の会社に動物を返しません。 </li><li>神経障害性疼痛の開発に先制鎮痛効果を回避するために、手術後の痛みのために鎮痛を管理していません。 </li></ol> 3.行動試験手順<ol><li>ラットは手術前の検査の前に住宅事情に少なくとも8日間順応できるようにします。 </li><li>手術前の検査前に少なくとも一日一回3日間の試験手順にラットを慣らします。 </li><li> 60 W赤い電球が提供する光で暗い部屋での行動試験は、試験領域の中心を照らすが、薄暗い部屋と暗いの残りの部分周囲を残しての中心の上に1メートルを停止しました。 </li><li>突然の聴覚刺激からの干渉を減少させるのに十分なバックグラウンドノイズがあることを確認してください。必要に応じて、ホワイトノイズを提供します。 </li><li>顔グルーミング行動の観察<ol><li> T寝具なしで覆われたプラスチックケージ内の試験室にコロニーから1匹のラットをransport。注：理想的には、これは最小限の外部刺激との短い旅行であるべきです。 </li><li>寝具なしでカバーし、透明なプラスチックケージにラットを置き（縦x幅x高さ：24センチメートルX 14センチメートル×17 cm）のバックビデオカメラの前でミラーリングされています。 </li><li>動物の行動の10分の記録を行います。記録時には、必ず実験者は試験室に存在しないことを確認してください。 </li><li>次の動物を配置する前に観察ケージを清掃してください。 </li><li>記録動作がラットの実験条件に盲目である実験者によって分析されていることを確認します。 </li><li> 10分の記録時に各顔グルーミングエピソードを記録します。注：顔のグルーミングは、前足が顔領域と接触している移動パターンとして定義されます。 </li><li>顔グルーミング行動の2つのタイプの区別を行います。シーケンスは、先行でもなく続いもされていない場合グルーミング体（すなわち、顔以外の身体部位の毛づくろい）を単離し、顔のグルーミングなどのエピソードを分類します。ボディグルーミング顔のグルーミングの直前または直後に実行された場合、ボディグルーミング中にグルーミング顔としてのエピソードを分類します。 </li><li>顔グルーミングエピソードの数を決定します。 <ol><li>イントラエピソード空間として4秒を超えていない顔グルーミングアクション間の時間を分類（ すなわち 、単一エピソード内の顔グルーミングアクション間の一時停止）。 </li><li>インターエピソード空間（ すなわち 、2つのエピソードの間に顔グルーミング行動の完全な中断）として4秒を超えて顔グルーミング行動との間の時間を分類。 </li></ol></li></ol></li><li>機械的刺激試験<ol><li>寝具で覆われたケージ内の試験室への植民地から最大6匹の動物の群における輸送ラット。これは最小限の外部刺激との短い旅行であることを確認してください。 </li><li>置き個別寝具透明なプラスチックケージのラット：ヒンジ付きふた付き（縦x幅x高さ24センチメートル×14センチ×17センチ）は、それが簡単に開閉できるようにします。 </li><li> 5フォン・フレイ毛の段階的なシリーズを使用してください。注：毛を曲げるのに必要な力は、0.015グラム、0.127グラム、0.217グラム、0.745グラムおよび2.150 gです。 </li><li>観察ケージにラットを慣らすし、10分間の動きに達します。 30秒ごとに、ふたを開け、ゆっくりとプラスチックの棒でケージの壁をタッチします。 </li><li>動物は（ すなわち、4本の足が地面に置いて、どちらも移動も凍結が、行動をスニッフィング示す）盗聴/無運動状態にある場合に、感覚毛パッドの中央付近にイオン領土内の第1のvon Frey毛を適用、mystacial鼻毛を取り巻く毛深い肌に。 </li><li>次の応答カテゴリ4のいずれかに属するように、刺激に対する動物の反応をスコア。 <ol><li>応答の完全な欠如を分類スコア0。 </li><li>スコア1（すなわち、ラットが刺激オブジェクトとその後探求される刺激物に向かって頭を回す）刺激検出を分類。 </li><li>撤退の反応を分類（ すなわち 、ラットはゆっくりと頭を回転させるか、活発に後方刺激が印加されると、時々 、単一の顔が刺激された領域と同側のワイプそれを引っ張る発生）としてスコア2。 </li><li> （エスケープ/攻撃応答を分類すなわち 、ラットは、または積極的に、刺激対象を攻撃することによって、ケージの壁に身をかがめる位置をとるように刺激する物体から離れて体を動かすことにより、受動的に、刺激物とのさらなる接触を回避かむとスコア3のような）動きをつかみます。 </li><li>グルーミング非対称顔分類スコア4として（ すなわち 、ラットは、刺激された顔領域に向けられた少なくとも3洗顔ストロークの途切れないシリーズが表 ​​示されます）。 </li><li>それぞれの動物の中では、STIMUを適用強度の低い順に李。刺激強度は、一方の側に適用された後、次の刺激強度に移動する前にもう一方の側に適用します。同側と反対側が刺激される順番をランダム。動物が各刺激の前に盗聴/無運動状態になければならないことに注意してください。 </li></ol></li></ol></li></ol>

<ol>
	<li>Jensen, T. S., Gottrup, H., Sindrup, S. H., Bach, F. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+clinical+picture+of+neuropathic+pain.">The clinical picture of neuropathic pain.</a> Eur J Pharmacol. 429 (1-3), 1-11 (2001).</li><li>Meyer Rosberg, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropathic+pain+a+multidimensional+burden+for+patients.">Neuropathic pain a multidimensional burden for patients.</a> Eur J Pain. 5 (4), 379-389 (2001).</li><li>Meyer Rosberg, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+the+SF+36+and+Nottingham+Health+Profile+in+patients+with+chronic+neuropathic+pain.">Comparison of the SF 36 and Nottingham Health Profile in patients with chronic neuropathic pain.</a> Eur J Pain. 5 (4), 391-403 (2001).</li><li>Vos, B. P., Strassman, A. M., Maciewicz, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+evidence+of+trigeminal+neuropathic+pain+following+chronic+constriction+injury+to+the+rats+infraorbital+nerve.">Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rats infraorbital nerve.</a> J Neurosci. 14, 2708-2723 (1994).</li><li>Clavelou, P., Pajot, J., Dallel, R., Raboisson, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+the+formalin+test+to+the+study+of+orofacial+pain.">Application of the formalin test to the study of orofacial pain.</a> Neurosci Lett. 103, 349-353 (1989).</li><li>Vos, B. P., Hans, G., Adriaensen, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+assessment+of+facial+pain+in+rats+face+grooming+patterns+after+painful+and+non-painful+sensory+disturbances+in+the+territory+of+the+rats+infraorbital+nerve.">Behavioral assessment of facial pain in rats face grooming patterns after painful and non-painful sensory disturbances in the territory of the rats infraorbital nerve.</a> Pain. 76 (1-2), 173-178 (1998).</li><li>Deseure, K. R., Adriaensen, H. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+between+two+types+of+behavioral+variables+of+non+evoked+facial+pain+after+chronic+constriction+injury+to+the+rat+infraorbital+nerve.">Comparison between two types of behavioral variables of non evoked facial pain after chronic constriction injury to the rat infraorbital nerve.</a> Comp Med. 52 (1), 44-49 (2002).</li><li>Deseure, K., Adriaensen, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonevoked+facial+pain+in+rats+following+infraorbital+nerve+injury+a+parametric+analysis.">Nonevoked facial pain in rats following infraorbital nerve injury a parametric analysis.</a> Physiol Behav. 81 (4), 595-604 (2004).</li><li>Deseure, K., Hans, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+study+of+non+evoked+orofacial+pain+following+different+types+of+infraorbital+nerve+injury+in+rats.">Behavioral study of non evoked orofacial pain following different types of infraorbital nerve injury in rats.</a> Physiol Behav. 138, 292-296 (2015).</li><li>Deseure, K., Koek, W., Adriaensen, H., Colpaert, F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+administration+of+the+5+hydroxytryptamine1A+agonist+(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)+-amino]-methyl]piperidin-1-yl]-methadone+(F+13640)+attenuates+allodynia+like+behavior+in+a+rat+model+of+trigeminal+neuropathic+pain.">Continuous administration of the 5 hydroxytryptamine1A agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl]piperidin-1-yl]-methadone (F 13640) attenuates allodynia like behavior in a rat model of trigeminal neuropathic pain.</a> J Pharmacol Exp Ther. 306 (2), 505-514 (2003).</li><li>Zimmerman, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ethical+Guidelines+for+investigations+of+experimental+pain+in+conscious+animals.">Ethical Guidelines for investigations of experimental pain in conscious animals.</a> Pain. 16, 109-110 (1983).</li><li>Mogil, J. S., Crager, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+should+we+be+measuring+in+behavioral+studies+of+chronic+pain+in+animals.">What should we be measuring in behavioral studies of chronic pain in animals.</a> Pain. 112 (1-2), 12-15 (2004).</li><li>Backonja, M. M., Stacey, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropathic+pain+symptoms+relative+to+overall+pain+rating.">Neuropathic pain symptoms relative to overall pain rating.</a> J Pain. 5 (9), 491-497 (2004).</li><li>Imamura, Y., Kawamoto, H., Nakanishi, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+heat+hyperalgesia+in+an+experimental+trigeminal+neuropathy+in+rats.">Characterization of heat hyperalgesia in an experimental trigeminal neuropathy in rats.</a> Exp Brain Res. 116, 97-103 (1997).</li><li>Chichorro, J. G., Zampronio, A. R., Souza, G. E., Rae, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orofacial+cold+hyperalgesia+due+to+infraorbital+nerve+constriction+injury+in+rats+reversal+by+endothelin+receptor+antagonists+but+not+non+steroidal+anti+inflammatory+drugs.">Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs.</a> Pain. 123 (1-2), 64-74 (2006).</li><li>Kramer, P. R., Bellinger, L. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Meal+Duration+as+a+Measure+of+Orofacial+Nociceptive+Responses+in+Rodents.">Meal Duration as a Measure of Orofacial Nociceptive Responses in Rodents.</a> J Vis Exp. (83), e50745 (2014).</li><li>Rossi, H. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+bilateral+trigeminal+constriction+injury+using+an+operant+facial+pain+assay.">Characterization of bilateral trigeminal constriction injury using an operant facial pain assay.</a> Neuroscience. 224, 294-306 (2012).</li><li>Anderson, E. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+the+Operant+Orofacial+Pain+Assessment+Device+(OPAD)+to+Measure+Changes+in+Nociceptive+Behavior.">Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior.</a> J Vis Exp. (76), 50336 (2013).</li></ol>

The authors have nothing to disclose.

イオンCCIモデルの最も興味深い側面は、それが自発的、非誘発（神経障害性）の痛みのユニークな指標を提供することです。脊髄神経モデルを使用して、神経因性疼痛のほとんどの動物研究は、もっぱら機械的または熱的刺激12への過敏性を反映して、侵害防御行動（ 例えば 、発声および離脱応答）を扱います。しかし、患者における主任臨床苦情が継続的な痛みではなく、?...

体性感覚神経の損傷は、ほとんどの場合、感覚の喪失につながります。これは非常によく理解理由及び方法は、いくつかの例では、末梢神経損傷は、慢性疼痛をもたらすされていません。その結果、痛みを伴う神経障害は、1の治療と生活2-3の患者の質の大幅な削減をもたらすのに困難な状態のまま。動物モデルは、既存および新たに開発された薬剤の有効性を検討すると神経因性疼痛の開発と維持に関与する病態生理学的メカニズムを識別するために重要なツールです。翻訳の痛みの研究のための主要な課題の中で識別され、（動物で自発痛を測定する、すなわち 、生理学的、急性被験者の基底状態に重畳された刺激をプロービングでチャレンジされていない動物における疼痛の存在を示す行動や他の症状）。この手順の全体的な目標は、外科的に誘導することです両方の自発的なの発展につながると三叉神経因性疼痛およびその治療に関与するメカニズムを研究するために使用することができます侵害防御行動を誘発ラットにおける眼窩下神経損傷。 監督、分離された顔のグルーミングは、ラットにおける自発性神経障害性疼痛のユニークな尺度です。眼窩下神経の慢性狭窄損傷（CCI）（イオン）後、ラットは、自発的な行動の持続的な痛みや機械的異痛4の指標である触覚刺激に応答して、変化を示します。 ION-CCI後、ラットは主に神経損傷イオンの領土に向け洗顔ストロークで、 すなわち 、活動をグルーミング増加し、非対称の顔を示しています。顔の侵害刺激（例えば、ホルマリン注射）5とは対照的に、非痛みを伴う感覚障害（ すなわち、一方的な鼻毛クリッピング、麻酔眼窩下神経ブロック、VIBRIの鉱物油の適用SSAE）ではないか、非常に簡単に（ すなわち 、発症後最初の数分間は）行動6グルーミング顔に大きな変化を誘導しました。これは、ION-CCI後にこの異常なグルーミングが負傷した神経領土の自然、強く嫌悪感の行動発現であると結論されました。イオンCCIラットにおけるこの動作は、患者において観察自発痛に強い似ています。さらなる研究は、イオンCCIによって大部分が影響を受けないまま行動グルーミング、より一般的な体（ すなわち、「グルーミング体中にグルーミング顔」）の一部である行動グルーミング顔、そして先行でもない侵害防御顔のグルーミングの重要な違いを識別しました大幅イオンCCI 7-9の後に増加されるグルーミング体（ すなわち、「単離された顔のグルーミング」）、続きます。薬理学的に、ボディグルーミング中グルーミング顔（非特異的薬剤効果の優れた制御測定を構成します<em運動機能を損なう可能性がある&gt;例えば、鎮静）。顔のグルーミングの2つのタイプの間の前肢の動きはまったく同じです。 ION-CCIは、ラットはまた、機械的異痛4、10の指標である触覚刺激に応答して変化を示す従うこと。ION-CCI後の最初の週（複数可）の間、ラットはもはや軽度または中等度の触覚（ すなわち、フォン・フレイに応答しません）刺激。この低応答性は、その後、突然でも非常に弱い刺激強度が侵害防御行動を誘発することにより、極端な過敏症に置き換えられます。過敏性の発症は、ラットの間で変動し得るが、術後3〜4週間後にほとんどのラットは、過反応性となっています。

<table border="0" cellpadding="0" cellspacing="0">
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		<tr>
			<td>Chromic catgut</td>
			<td>Dynek&#160;</td>
			<td>CG504</td>
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			<td>Nembutal&#160; (pentobarbital)</td>
			<td>Pharmacy</td>
			<td></td>
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			<td>Atropine</td>
			<td>Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Clippers for small animals - Favorita II</td>
			<td>Aesculap</td>
			<td>GT104</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereotaxic instrument</td>
			<td>Stoelting</td>
			<td>51600</td>
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			<td>Ophthalmic ointment (Liposic)</td>
			<td>Pharmacy</td>
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			<td>Homeothermic monitor system</td>
			<td>Harvard Apparatus</td>
			<td>PY8 50-7221-F</td>
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			<td>Cotton applicator</td>
			<td>Pharmacy</td>
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			<td>Precision cotton swab</td>
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			<td>Operation microscope</td>
			<td>Kaps</td>
			<td>SOM 62</td>
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			<td>Dumont #5 forceps</td>
			<td>Fine Science Tools</td>
			<td>11251-10</td>
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			<td>Dumont forceps - Micro-blunted tips (#5/45)</td>
			<td>Fine Science Tools</td>
			<td>11253-25</td>
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			<td>Scissors - blunt tips</td>
			<td>Fine Science Tools</td>
			<td>14574-09</td>
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			<td>Polyester sutures - Mersilene (4-0)</td>
			<td>Ethicon</td>
			<td>R871H</td>
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			<td>Digital video camera</td>
			<td>Sony</td>
			<td>HDR-CX330E</td>
			<td></td>
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			<td>Semmes-Weinstein Von Frey Aesthesiometer kit</td>
			<td>Stoelting</td>
			<td>58011</td>
			<td></td>
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chronic constriction injury of the rat's infraorbital nerve (ion-cci) to study trigeminal neuropathic pain

動物モデルは、神経因性疼痛の病態生理と薬理学を研究するための重要なツールです。本稿では、ラットにおいて、三叉神経因性疼痛を研究するために、外科的および行動の手順を説明します。三叉神経因性疼痛症候群の特異性を満たすために、眼窩下神経（イオン）が緩く神経を結紮することによって慢性狭窄損傷（CCI）に供されます。イントラ軌道アプローチが露出し、眼窩内のイオンを連結するためにここに提示されています。イオンライゲーションの後、ラットは、自発的な行動の持続的な痛みや機械的異痛の指標であるフォン・フレイ毛の刺激に応答して、変化を示します。二つの相は、行動の変化の開発に定義することができます。 ION-CCI（フェーズ1）以下の最初の週の間、ラットは主に神経損傷イオンの領土に向け洗顔ストロークで、すなわち 、活動をグルーミング増加し、非対称の顔を示しています。違いは、顔グラムの間で行われますION-CCIによって大幅に影響を受けないまま、より一般的なボディグルーミング行動の一部である行動をooming、顔はそれが先行することも、かなりのイオンCCI後に増加されたボディグルーミング、続いもされていないグルーミング。この期間中、イオン領土の機械的刺激に対する応答性が低下します。この反応性低下が急激であっても非常に弱い刺激強度が侵害防御行動（フェーズ2）を誘発することにより、極端な過敏症に置き換えられます。これらの行動の変化の間の現象学的類似点と顔面痛（ すなわち、顔の侵害刺激に対する応答）の兆候を報告したライゲーションされたイオンの領土で異常感覚/知覚異常や機械的異痛の存在を示唆しています。

イオンCCIラットは、孤立した顔グルーミング（ 図1）に費やされた時間の量に強い術後の増加を示します。増加の最初の術後週の終わりにピークとし、次の週の間に減少します。最近の研究では、大幅に3つまでの週間増加するグルーミング顔を発見しました。偽手術ラットで顔グルーミング行動は、多かれ少なかれ影響を受けません。 イオンCCIラットは、第...

Watch this Scientific Journal Video about Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain at JoVE.com

Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat&#8217;s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia.

三叉神経因性疼痛を研究するためにラットの眼窩下神経の慢性狭窄傷害（ION-CCI）

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral ...

chronic-constriction-injury-rat-s-infraorbital-nerve-ion-cci-to-study

Research

JoVE Journal

Medicine

Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study Trigeminal Neuropathic Pain

19.3K ビュー.  University of Antwerp. This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat’s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia. 

ビデオ: Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

同所性大動脈移植：慢性血管障害の発生研究のラットモデル

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

医学

The Spared Nerve Injury (SNI) Model of Induced Mechanical Allodynia in Mice

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared nerve injury (SNI) model induces symptoms of neuropathic pain such as mechanical allodynia i.e. pain due to tactile stimuli that do not normally provoke a painful response [1]. 
The SNI mouse model involves ligation of two of the three branches of the sciatic nerve (the tibial nerve and the common peroneal nerve), while the sural nerve is left intact [2]. The lesion results in marked hypersensitivity in the lateral area of the paw, which is innervated by the spared sural nerve. The non-operated side of the mouse can be used as a control. The advantages of the SNI model are the robustness of the response and that it doesn&#x2019;t require expert microsurgical skills.
The threshold for mechanical pain response is determined by testing with von Frey filaments of increasing bending force, which are repetitively pressed against the lateral area of the paw [3], [4]. A positive pain reaction is defined as sudden paw withdrawal, flinching and/or paw licking induced by the filament. A positive response in three out of five repetitive stimuli is defined as the pain threshold. 
As demonstrated in the video protocol, C57BL/6 mice experience profound allodynia as early as the day following surgery and maintain this for several weeks.

The Spared Nerve Injury SNI Model of Induced Mechanical Allodynia in Mice

The Spared Nerve Injury animal model is described here as a mouse model of peripheral neuropathic pain following partial denervation of the sciatic nerve by lesioning the tibial and common peroneal nerve branches, leaving the remaining sural nerve intact. Behavioral modification resulting from mechanical allodynia is quantified by von Frey filaments.

マウスで誘導機械的異痛症の倹約神経損傷（SNI）モデル

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared ...

Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of the population1,2. Symptoms include spontaneous (tingling, burning, electric-shock like) pain, dysaesthesia, paraesthesia, allodynia (pain resulting from normally non-painful stimuli) and hyperalgesia (an increased response to painful stimuli). The sensory symptoms are co-morbid with behavioural disabilities, such as insomnia and depression. To study chronic neuropathic pain several animal models mimicking peripheral nerve injury have been developed, one of the most widely used is Bennett and Xie's (1988) unilateral sciatic nerve chronic constriction injury (CCI)3 (Figure 1). Here we present a method for performing CCI and testing pain hypersensitivity.
CCI is performed under anaesthesia, with the sciatic nerve on one side exposed by making a skin incision, and cutting through the connective tissue between the gluteus superficialis and biceps femoris muscles. Four chromic gut ligatures are tied loosely around the sciatic nerve at 1 mm intervals, to just occlude but not arrest epineural blood flow. The wound is closed with sutures in the muscle and staples in the skin. The animal is then allowed to recover from surgery for 24 hrs before pain hypersensitivity testing begins.
For behavioural testing, rats are placed into the testing apparatus and are allowed to habituate to the testing procedure. The area tested is the mid-plantar surface of the hindpaw (Figure 2), which falls within the sciatic nerve distribution. Mechanical withdrawal threshold is assessed by mechanically stimulating both injured and uninjured hindpaws using an electronic dynamic plantar von Frey aesthesiometer or manual von Frey hairs4. The mechanical withdrawal threshold is the maximum pressure exerted (in grams) that triggers paw withdrawal. For measurement of thermal withdrawal latency, first described by Hargreaves et al (1988), the hindpaw is exposed to a beam of radiant heat through a transparent glass surface using a plantar analgesia meter5,6. The withdrawal latency to the heat stimulus is recorded as the time for paw withdrawal in both injured and uninjured hindpaws. Following CCI, mechanical withdrawal threshold, as well as thermal withdrawal latency in the injured paw are both significantly reduced, compared to baseline measurements and the uninjured paw (Figure 3). The CCI model of peripheral nerve injury combined with pain hypersensitivity testing provides a model system to investigate the effectiveness of potential therapeutic agents to modify chronic neuropathic pain. In our laboratory, we utilise CCI alongside thermal and mechanical sensitivity of the hindpaws to investigate the role of neuro-immune interactions in the pathogenesis and treatment of neuropathic pain.

Due to the simplicity of surgery and the robust behavioural outcome, chronic constriction of the sciatic nerve is one of the pre-eminent animal models of neuropathic pain. Within 24 hrs following surgery, pain hypersensitivity is established and can be quantitatively measured using a von Frey aesthesiometer (mechanical test) and plantar analgesia meter (thermal test).

ラットの坐骨神経と疼痛過敏テストの慢性的なくびれ

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of ...

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Breathing-controlled Electrical Stimulation BreEStim for Management of Neuropathic Pain and Spasticity

The purpose is to present a new method, breathing-control electrical stimulation (BreEStim) for management of neuropathic pain and spasticity.

神経因性疼痛、痙縮の管理のための呼吸制御型電気刺激（BreEStim）

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

マウスの膀胱痛に対するモデルとしての膀胱膨満誘発内臓運動応答

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the &#34;cuff model&#34; of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

Neuropathic pain is a consequence of a lesion or disease affecting the somatosensory system. The &#8220;cuff model&#8221; of neuropathic pain in mice consists of the implantation of a polyethylene cuff around the main branch of the sciatic nerve. Mechanical allodynia is tested using von Frey filaments.

マウスにおける神経因性疼痛の坐骨神経細胞浸潤モデル

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in ...

Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration.

We present a surgical protocol detailing how to perform a cut or crush axotomy on the facial nerve in the mouse. The facial nerve axotomy can be employed to study the physiological response to nerve injury and test therapeutic techniques.

マウスにおける顔面神経軸索切断：傷害に運動ニューロン応答を研究するためのモデル

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and ...

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed.
This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

Treating chronic or neuropathic facial pain can be challenging when medical or standard treatment fails. Subcutaneous nerve field stimulation is the least invasive form of neuromodulation and is used for chronic back pain. We applied this technology to treat chronic and neuropathic trigeminal facial pain.

難治性顔面痛のための皮下三叉神経刺激

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. ...

Development of Recombinant Proteins to Treat Chronic Pain

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates for treating debilitating pain conditions due to their capacity to regulate aberrant neuro-immune interactions. However, physiologically they work in a network of various cytokines, and therefore their therapeutic effect may not be optimal when used as stand-alone drugs. To overcome this limitation, we developed a fusion protein of the anti-inflammatory cytokines IL4 and IL10. Here, we describe the methods for production and quality control of IL4-10 recombinant fusion protein and we test the effectiveness of the IL4-10 fusion protein to resolve pain in a mouse model of persistent inflammatory pain.

In this paper we provide details for the methods of production and quality control of an IL4-10 recombinant fusion protein. We also show how to test the effectiveness of this protein to resolve pain in a mouse model of inflammatory pain.

慢性的な痛みの治療に遺伝子組換えタンパク質の開発

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates ...

Employing the Forced Oscillation Technique for the Assessment of Respiratory Mechanics in Adults

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and diseased individuals. FOT, a complementary method to traditional pulmonary function testing, utilizes a range of oscillatory frequencies superimposed on tidal breathing to measure the functional relationship between airway pressure and flow. This passive assessment provides an estimate of respiratory system resistance (Rrs) and reactance (Xrs) that reflect airway caliber and energy storage and dissipation, respectively. Despite the recent increase in popularity and updated Technical Standards, clinical adoption has been slow which relates, in part, to the lack of standardization regarding the acquisition and reporting of FOT data. The goal of this article is to address the lack of standardization across laboratories by providing a comprehensive written protocol for FOT and an accompanying video. To illustrate that this protocol can be utilized irrespective of a particular device, three separate FOT devices have been employed in the case examples and video demonstration. This effort is intended to standardize the use and interpretation of FOT, provide practical suggestions, as well as highlight future questions that need to be addressed.

As the use of forced oscillation technique (FOT) is increasingly utilized to characterize respiratory mechanics, there is a need to standardize methods with respect to nascent technical guidelines and various manufacturer's recommendations. A detailed protocol is provided including FOT assessment and interpretation for two cases to facilitate the standardization of methods.

成人の呼吸力学の評価のための強制振動技術の採用

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and ...