著者らは、ベネットと謝（1988）によってCCIモデルの元の説明を確認したいと思います。 この作品は、GMTに科学と医学研究のための国民健康、オーストラリアの医学研究評議会（ID＃568637）とNSW事務局からの補助金によって部分的にサポートされていました。

1。坐骨神経の慢性くびれ無菌テクニックは外科的処置に使用する必要があります。 70％エタノールで手術の作業面を消毒し、オートクレーブで滅菌し、事前の機器（例えば、微細なハサミ、鉗子、およびトラクター）、ガーゼ、ステープルと綿棒で準備します。複数の手術については、70％エタノールまたはラットの間に乾燥したビーズ滅菌器と楽器をきれいにし、resterilise。手術用マスク、ヘアボンネットと滅菌手袋を着用する必要があります。 神経の収縮のために、乾燥を防ぐために、滅菌生理食塩水に浸漬し、約3 cmの長さの小片にそれを切断することによりクロム腸縫合糸を準備します。傷を閉じるため、市販の滅菌絹縫合糸を使用しています。 <ol><li> O 2におけるイソフルランの5％を使用した誘導チャンバ内にラットを麻酔をかけるし、フェイスマスク、カスタムメイドを経由してO 2にイソフルラン2％を提供し、手順の実行中にanesthetised動物を監視する。一般的な代替麻酔薬はハロタンまたはペントバルビタール腹腔内ナトリウムを吸入されています。これらの受容体は神経因性疼痛の開発において重要であるので、N-メチル-D-アスパラギン酸（NMDA）受容体拮抗薬としてケタミンは、避けるべきである。 </li><li>ラットの左後肢を剃る。その後、37℃の熱安定化された加熱マットの上に動物を配置°Cと目に潤滑眼軟膏を適用します。 </li><li> 70％イソプロピルアルコールとヨウ素溶液の3つの代替アプリケーションで剃毛面積を滅菌する。 </li><li>その胸/胸の上に横たわったラットと、左後肢を高め、足にマスキングテープを使用して、背骨に対して90°にfemorの位置に保持します。 </li><li>皮膚と平行に切開が、femor以下3〜4ミリメートルを作成し、結合組織を切断することによって切開を周囲の筋肉から皮膚を解放します。 </li><li>臀筋浅上腕二頭筋との間に結合組織を切って鈍いはさみを使用して、大腿の筋肉。 </li><li>坐骨神経の明確な可視化を可能にする、二つの筋肉の間のギャップを広げるためにトラクターを使用しています。 </li><li>湾曲した平滑末端先端鉗子、マイクロはさみを使用して、そっとフリー周囲の結合組織からの坐骨神経（坐骨三つの部分に分かれることに近位）の約10ミリメートル。 </li><li>顕微鏡と良好な光源下で、坐骨神経の三分割に近ダブルノットを持つ4つの合字（クロム腸4.0、エチコン、米国）、間隔を1 mm、接続します。各字では、単一の緩いループを開始し、ループに近い両端をつかみ、ループがかろうじてぴったりされており、合字は、神経に沿ってスライドしなくなるまで締めます。その適切な位置にループを保持するために、結び目を完了する最初の上に2番目のループを配置します。最後に、約1ミリメートルの字の緩い端をカット。神経の収縮は最小限である、と簡単な筋が観察された場合には直ちに停止し、thの逮捕を防ぐため必要があります電子神経鞘の血流。字を締めすぎると軸索切断につながり、成功した疼痛過敏テストを排除する自切（自傷）は、両方の不要な副作用。 </li><li>皮膚を固定する筋層とステープル（Autoclip、9 mm）を閉じるために縫合糸（Mersilk 5.0、エチコン）を使用します。次に、傷口を滅菌するためにヨウ素溶液（Riodine）を使用します。 </li><li>窒息無意識の動物を防ぐために、麻酔の回復期間中に密接にラットを観察し、それは平らな紙の寝具（ない標準的な畜産ベッド）を持つ別のケージに回復することができます。 すべての術後鎮痛の捜査を与える前に、これは疼痛過敏テストを妨げる可能性があるという事実を考慮する必要があります。実際には、負傷時の麻酔薬、リドカイン、ローカルのアプリケーションは、神経因性疼痛の開発を変更し、前の週7の痛覚過敏の程度を減少させることができるという証拠がある。このmのさらなる議論のためにBennett ら 8でレビューをアッター湖。 </li></ol> 2。痛みの挙動の測定<ol><li>実験を開始する前に、数日間のラットの毎日の処理は、そのハンドラにラットを慣らすストレスやかむのリスクを軽減するために推奨されます。 </li><li>行動試験の前に、ラットは、試験手順や動物のエンクロージャに慣らさする必要があります。テスト環境は、一定の温度と湿度、静かでよく制御され保持され、各テストセッション日の同様の時間で実施する必要があります。 </li><li>疼痛過敏テストは必要に応じて、CCI（ベースライン）の前と後のCCIの異なる時点で複数回実行する必要があります。 </li></ol> 3。機械逃避閾値<ol><li>テストの日に、場所ラット上昇メッシュ床試験ケージに撤退のしきい値を測定する前に、15〜30分、ケージの探査とgrooを許可する明は、活動を中止し、ラットはリラックスして静止になること。 </li><li>動的足底·フォン·フレイ角膜知覚計（ウーゴ·バジーレ、イタリア）を使用して、金属メッシュを避けて、後足の半ばに底表面直下にフィラメントとタッチ刺激ユニットを配置し、スタートキーを押します。これは機械的に増加させる力と後足の足底表面を刺激するフィラメントを持ち上げる。 </li></ol>マニュアル·フォン·フレイ毛は、皮膚に適用されたときに特定の力を誘発するために校正されて拡径フィラメントのシリーズです。それらは前述のように足引っ込め閾値を測定するための電子ダイナミック足·フォン·フレイの角膜知覚計、4の代替として使用することができます。エレクトロニック·フォン·フレイaesthesiometers（例えばIITC、アメリカ、Somedic、スウェーデン）のいくつかの代替メーカーもあります。 <ol start="3"><li>負傷したと無傷の両方hindpaから機械的な撤退のしきい値を記録フォークリフト、順番にWS、。このデバイスは、足に圧力を適用し、撤退の反応時にシステムが自動的に記録し、（グラム）を適用し最大の力を表示します。あいまいな応答（歩行やグルーミングの場合はIE）が発生した場合、刺激を繰り返してしきい値を記録します。ブーツまたは後足に続く刺激の揺れは、痛みに関連付けられた動作の兆候です。 </li><li>刺激の間に約5分の間隔で機械的な刺激を3回繰り返して、しきい値を記録し、足撤退のしきい値の平均値を計算します。 </li></ol> 4。熱の撤退の待ち時間足底のテスト機器の赤外線（IR）の熱強度が実験を開始する前に調整する必要があります。私たちの研究室では、ナイーブなラットでは約10秒間の平均足撤退の待ち時間を与えるために、IRの強度を調整し、我々は組織のダムを避けるために、20秒でカットオフ遅延時間を設定する足の削除に失敗した場合の年齢。 <ol><li>テストの日に、場所の15〜30分の待ち時間を測定する前に、ガラス床のテストケージにラットでは、ケージの探査を可能にし、停止するための活動をグルーミングし、ラットはリラックスして静止になっています。 </li><li>熱足鎮痛装置（ウーゴ·バジーレ、イタリア）を使用して、直接、後足の半ばに底表面の下に赤外線源を配置し、スタートキーを押します。これは透明なガラス表面からの放射熱のビームに後足の足底表面を公開しています。熱足鎮痛機器（例えばIITC、アメリカ、Stoelting、アメリカ）の代替メーカーもあります。 </li><li>フォークリフト、の順序で、負傷したと無傷の両方の後肢からの撤退の待ち時間を記録します。このデバイスは自動的に熱源から足の撤退への熱刺激の発症から（秒単位）にかかった時間を記録します。あいまいな応答が発生した場合（ambulaの場合、すなわちる、またはグルーミング）、刺激を繰り返して待ち時間を記録します。ブーツまたは後足に続く刺激の揺れは、痛みに関連付けられた動作の兆候です。 </li><li>熱刺激の刺激の間に約5分の間隔で少なくとも3回繰り返し、レイテンシを記録し、足撤退の待ち時間の平均値を計算します。 </li></ol> 4。代表的な結果 Wistarラットの同側（負傷）と対（無傷の）足の機械逃避閾値と熱回収の遅延の例は、 図3A、図3Bに示すように前（ベースライン）および2-12日CCIした後に発生します。これらの図から、それはCCIは、機械的および熱的疼痛過敏症の存在を示す、機械的な撤退のしきい値と同側の後足の熱離脱レイテンシの両方で有意な減少を引き起こしていることが分かる慢性神経因性疼痛の両方の機能<html> 。 <img alt="図1" src="/files/ftp_upload/3393/3393fig1.jpg" /> 図1。CCIモデルの字の位置を示す概略図。神経因性疼痛のこの動物モデルは半ば腿レベルでの坐骨神経の4つの緩いクロム腸の字の配置が含まれます。これは、後足の足とその後の疼痛過敏に行く求心性の一部のみを負傷し、その結果。 <img alt="図2" src="/files/ftp_upload/3393/3393fig2.jpg" /> 図2痛みのテストに使用後足エリアの図。ように赤い点線の円で示された足蹠にちょうど後部半ばに底表面は、痛みのテストに使用されています。この領域は、坐骨神経の末端の枝で主に支配されています。かかとと足蹠は、差動皮膚の感度のために避けるべきである。 3.JPG &quot;/&gt; ラットの坐骨神経の慢性収縮以下の図3。疼痛過敏。無傷の（反対）後足（P &lt;0.01反復測定2に比べて（B）負傷した（同側）後足の熱刺激に対するCCI後、足引っ込め閾値の有意な減少は、機械的な刺激（）と足撤退の待ち時間にあります一方向ANOVA）。データは平均±SEM、n = 7のWistarラットを示しています。

<ol>
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M., Stuesse, S. L., Cruce, W. L., Crisp, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gender+and+the+behavioral+manifestations+of+neuropathic+pain.">Gender and the behavioral manifestations of neuropathic pain.</a> Pharmacol Biochem. Behav. 68, 99-104 (2001).</li><li>Chung, J. M., Choi, Y., Yoon, Y. W., Na, H. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+age+on+behavioral+signs+of+neuropathic+pain+in+an+experimental+rat+model.">Effects of age on behavioral signs of neuropathic pain in an experimental rat model.</a> Neurosci. Lett. 183, 54-57 (1995).</li><li>Tanck, E. N., Kroin, J. S., McCarthy, R. J., Penn, R. D., Ivankovich, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+age+and+size+on+development+of+allodynia+in+a+chronic+pain+model+produced+by+sciatic+nerve+ligation+in+rats.">Effects of age and size on development of allodynia in a chronic pain model produced by sciatic nerve ligation in rats.</a> Pain. 51, 313-316 (1992).</li><li>Shir, Y., Sheth, R., Campbell, J. N., Raja, S. N., Seltzer, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Soy-containing+diet+suppresses+chronic+neuropathic+sensory+disorders+in+rats.">Soy-containing diet suppresses chronic neuropathic sensory disorders in rats.</a> Anesth. Analg. 92, 1029-1034 (2001).</li><li>Yoon, Y. W., Lee, D. H., Lee, B. H., Chung, K., Chung, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+strains+and+substrains+of+rats+show+different+levels+of+neuropathic+pain+behaviors.">Different strains and substrains of rats show different levels of neuropathic pain behaviors.</a> Experimental Brain Research. 129, 167-171 (1999).</li><li>Mogil, J. S., Davis, K. D., Derbyshire, S. 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+necessity+of+animal+models+in+pain+research.">The necessity of animal models in pain research.</a> Pain. 151, 12-17 (2010).</li><li>Mogil, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+pain:+progress+and+challenges.">Animal models of pain: progress and challenges.</a> Nat. Rev. Neurosci. 10, 283-294 (2009).</li><li>Langford, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coding+of+facial+expressions+of+pain+in+the+laboratory+mouse.">Coding of facial expressions of pain in the laboratory mouse.</a> Nat. Methods. 7, 447-449 (2010).</li><li>Austin, P. J., Moalem-Taylor, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuro-immune+balance+in+neuropathic+pain:+involvement+of+inflammatory+immune+cells,+immune-like+glial+cells+and+cytokines.">The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines.</a> J. Neuroimmunol. 229, 26-50 (2010).</li></ol>

動物実験は、ニューサウスウェールズ州、オーストラリアの大学の動物のケアと倫理委員会によって承認され、痛みの研究のための国際協会によって発行されたガイドラインに従った。

CCIは、慢性神経因性疼痛の広く使われている末梢神経損傷モデルです。それは、実行するのは比較的簡単であり、受傷後少なくとも1ヶ月堅牢で安定した疼痛過敏を生成します。 CCIに続いて、ラット（つま先が一緒に開催し、足底、屈曲と足がeverted）負傷した後足の異常な姿勢を示し、同様に、振とう保護したり、自発痛9の存在を示唆して負傷した後足をなめることを繰り返す。感...

<table border="1"><tbody><tr><td> 試薬/装置の名前 </td><td> 会社 </td><td> カタログ番号 </td><td> コメント </td></tr><tr><td>クロム消化</td><td>エチコン</td><td> G-211 </td><td> 4から0までの厚さ</td></tr><tr><td>イソフルレン</td><td> Delvet Pty。株式会社、セブンヒルズ、NSW </td><td> N / A </td><td></td></tr><tr><td> Mersilk </td><td>エチコン</td><td> W-580 </td><td> 5から0までの厚さ</td></tr><tr><td> Autoclip </td><td>ベクトン·ディッキンソン</td><td> 427631 </td><td> 9ミリメートルのステンレス鋼</td></tr><tr><td> Riodine </td><td>オリオン</td><td> R1000802F </td><td>の1％w / vのヨウ素</td></tr><tr><td>熱足鎮痛機器</td><td>ウーゴ·バジーレ</td><td> 37370 </td><td></td></tr><tr><td>動的足底の角膜知覚計</td><td>ウーゴ·バジル電子</td><td> 37400 </td><td></td></tr></tbody></table>

chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats

慢性の神経因性疼痛は、中枢または末梢神経系への損傷に起因する、人口の1,2の7から18パーセントに影響を与え、流行と衰弱状態です。症状は、自発的（のようなうずき、燃焼、電気ショック）の痛み、dysaesthesia、感覚異常、アロディニア（痛みは通常は非痛み刺激に起因する）と痛覚過敏を（痛み刺激に対する応答の増加）が含まれています。感覚症状は、不眠やうつ病などの行動障害との併存である。慢性神経因性疼痛を勉強する末梢神経損傷を模倣するいくつかの動物モデルが開発されている、最も広く使用されているの一つは、ベネットと謝（1988年）一方的な坐骨神経の慢性狭窄損傷（CCI）3（ 図1）。ここでは、CCIとテストの疼痛過敏を実行するための手法を提案する。 CCIは、次のようにすることによって公開された一方の側の坐骨神経で、全身麻酔下で行われる親族切開し、中殿浅と大腿二頭筋の筋肉の間に結合組織を切断する。四クロム腸の字だけ閉塞するために、1ミリメートルの間隔で坐骨神経の周りにゆるく結んが神経鞘の血流を逮捕されていません。傷は皮膚の筋肉やステープルで縫合閉鎖しています。疼痛過敏症テストを開始する前に、動物は、その後24時間の手術から回復するために許可されています。 行動テストのために、ラットを試験装置に配置され、テスト手順に慣らすために許可されています。テストエリアは、坐骨神経の分布範囲内に後足の半ばに底表面（ 図2）です。機械的な撤退のしきい値は機械的に電子の動的足底のフォン·フレイ角膜知覚計またはマニュアル·フォン·フレイ毛4を使用して負傷し、無傷の後肢の両方を刺激することによって評価されています。機械的な撤退のしきい値は、作用する最大圧力です。（グラム）足の撤退をトリガします。第一ハーグリーブスら （1988）によって記述され、熱回収の遅延の測定については、後足は足鎮痛メーター5,6を使用して、透明なガラス表面からの放射熱のビームにさらされている。熱刺激に撤退レイテンシが負傷し、無傷の両方の後肢の足撤退のための時間として記録されます。以下CCI、負傷した足に機械的な撤退のしきい値と同様に、熱回収の遅延は、ベースラインの測定と無傷の足（ 図3）と比較して、両方とも大幅に減少しています。疼痛過敏症テストを組み合わせた末梢神経損傷のCCIモデルでは、慢性の神経因性疼痛を変更するには、潜在的な治療薬の有効性を検討するためのモデルシステムを提供します。私たちの研究室では、病因に神経免疫相互作用の役割を調べるために後肢の熱的、機械的な感度と一緒にCCIを活用神経因性疼痛の治療と。

Watch this Scientific Journal Video about Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats at JoVE.com

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

手術のシンプルかつ堅牢な行動の結果により、坐骨神経の慢性収縮は、神経因性疼痛の卓越した動物モデルの一つです。手術後24時間以内に、疼痛過敏症は、von Freyの角膜知覚計（機械試験）と足鎮痛メーター（温度試験）を使用して確立されており、定量的に測定することができます。

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 ...

chronic-constriction-sciatic-nerve-pain-hypersensitivity-testing

Research

JoVE Journal

Medicine

58.5K ビュー.  University of New South Wales. 手術のシンプルかつ堅牢な行動の結果により、坐骨神経の慢性収縮は、神経因性疼痛の卓越した動物モデルの一つです。手術後24時間以内に、疼痛過敏症は、von Freyの角膜知覚計（機械試験）と足鎮痛メーター（温度試験）を使用して確立されており、定量的に測定することができます。

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

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

ラット脊髄損傷後の急性および慢性の触覚官能検査

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

医学

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 ...

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

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral procedures to study trigeminal neuropathic pain in rats. To meet the specificity of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is subjected to a chronic constriction injury (CCI) by loosely ligating the nerve. An intra-orbital approach is presented here to expose and ligate the IoN in the orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are indicative of persistent pain and mechanical allodynia. Two phases can be defined in the development of the behavioral changes. During the first week following IoN-CCI (phase 1), rats show an increased and asymmetric face grooming activity, i.e., with face wash strokes primarily directed to the nerve-injured IoN territory. A distinction is made between face grooming behavior that is part of a more general body grooming behavior, which remains largely unaffected by IoN-CCI, and face grooming that is neither preceded nor followed by body grooming, which is significantly increased after IoN-CCI. During this period, responsiveness to mechanical stimulation of the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an extreme hyperresponsiveness whereby even very weak stimulus intensities provoke nocifensive behavior (phase 2). The phenomenological similarities between these behavioral alterations and reported signs of facial pain (i.e., responses to noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia and mechanical allodynia in the ligated IoN territory.

Chronic Constriction Injury of the Rat&#039;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 ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

ラットの腹部大動脈の収縮を通じて心臓リモデリングのモデル

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Minimally Invasive Transverse Aortic Constriction in Mice

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Minimally invasive transverse aortic constriction (MTAC) conserves the essentials of regular transverse aortic constriction (TAC) while eliminating the use of a ventilator with tracheal intubation. It proves to be a highly desirable method for high-throughput studies on left ventricular overload, particularly in translational studies.

マウスにおける低侵襲横大動脈狭窄

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard ...

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 ...

Osteoarthritis Pain Model Induced by Intra-Articular Injection of Mono-Iodoacetate in Rats

The current animal models of osteoarthritis (OA) can be divided into spontaneous models and induced models, both of which aim to simulate the pathophysiological changes of human OA. However, as the main symptom in the late stage of OA, pain affects the patients&#39; daily life, and there are not many available models. The mono-iodoacetate (MIA)-induced model is the most widely used OA pain model, mainly used in rodents. MIA is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, which causes chondrocyte death, cartilage degeneration, osteophyte, and measurable changes in animal behavior. Besides, expression changes of matrix metalloproteinase (MMP) and pro-inflammatory cytokines (IL1 &#946; and TNF &#945;) can be detected in the MIA-induced model. Those changes are consistent with OA pathophysiological conditions in humans, indicating that MIA can induce a measurable and successful OA pain model. This study aims to describe the methodology of intra-articular injection of MIA in rats and discuss the resulting pain-related behaviors and histopathological changes.

This study describes the method of intra-articular injection of mono-iodoacetate in rats and discusses the resulting pain-related behaviors and histopathological changes, which provide references for future applications.

ラットにおけるモノヨードアセテートの関節内注射により誘発される変形性関節症疼痛モデル

The current animal models of osteoarthritis (OA) can be divided into spontaneous models and induced models, both of which aim to simulate the ...

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. 
Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. 
To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.

Partial sciatic nerve ligation induces long-lasting chronic neuropathic pain, characterized by exaggerated responses to thermal and mechanical stimuli. This mouse model of neuropathic pain is commonly used to study innovative therapies for pain management. This article describes in detail the surgical procedure to improve standardization and reproducibility.

坐骨神経部分結紮術:新規治療法の抗侵害受容効果を研究するための慢性神経因性疼痛のマウスモデル

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. ...

ラットモデルにおけるFSN療法の改善:不快感の最小化と効率の最大化

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal&#39;s body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat&#39;s discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.

著者スポットライト:FSN治療の治療効果を明らかにする – 神経障害性疼痛における研究と臨床応用の橋渡し

We present a protocol for using Fu's subcutaneous needling in a chronic constriction injury model to induce sciatic nerve pain in rats.

坐骨神経痛に対するフー皮下ニードリングの有効性:慢性狭窄損傷ラットモデルにおける行動的および電気生理学的変化

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the ...