Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

We present an operant  system for the detection of pain in awake, conscious rodents. The Orofacial  Pain Assessment Device (OPAD) assesses pain behaviors ...

Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay

Pain has sensory and affective components. Unlike traditional, reflex-based pain assays, operant pain assays can produce more clinically relevant results ...

University of Florida College of Dentistry

University of Florida College of Medicine 

University of Florida, Gainesville

La m&#xE9;dula espinal N-metil-D-aspartato (NMDA) est&#xE1;n &#xED;ntimamente implicados en el desarrollo y mantenimiento de la sensibilizaci&#xF3;n central. Sin embargo, los mecanismos que median la funci&#xF3;n alterada de los receptores NMDA no son bien entendidos. En este estudio el papel de la fosforilaci&#xF3;n de las variantes de empalme NR1 y subunidades NR2 fue examinado despu&#xE9;s de la inflamaci&#xF3;n en la pata trasera ratas. Adem&#xE1;s, examin&#xF3; el nivel de expresi&#xF3;n de estas prote&#xED;nas despu&#xE9;s de la lesi&#xF3;n.

De la m&#xE9;dula espinal NR1 fosforilaci&#xF3;n de la serina y la represi&#xF3;n subunidad NR2B Tras la inflamaci&#xF3;n perif&#xE9;rica

&#x810A;&#x9AD3; N-&#x7532;&#x57FA;-D-&#x5929;&#x51AC;&#x6C28;&#x9178; (NMDA) &#x53D7;&#x4F53;&#x5BC6;&#x5207;&#x53C2;&#x4E0E;&#x5F00;&#x53D1;&#x548C;&#x7EF4;&#x62A4;&#x7684;&#x4E2D;&#x592E;&#x5BA3;&#x4F20;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x8C03;&#x89E3; NMDA &#x53D7;&#x4F53;&#x7684;&#x8680;&#x53D8;&#x7684;&#x4F5C;&#x7528;&#x7684;&#x673A;&#x5236;&#x8FD8;&#x4E0D;&#x592A;&#x6E05;&#x695A;&#x3002;&#x5728;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x7684; NR1 &#x62FC;&#x63A5;&#x6B3E;&#x5F0F;&#x53CA; NR2 &#x4E9A;&#x57FA;&#x78F7;&#x9178;&#x5316;&#x4F5C;&#x7528;&#x88AB;&#x5BA1;&#x67E5;&#x540E;&#x5927;&#x9F20;&#x540E;&#x817F;&#x722A;&#x5B50;&#x708E;&#x75C7;&#x3002;&#x6211;&#x4EEC;&#x8FDB;&#x4E00;&#x6B65;&#x7814;&#x7A76;&#x8FD9;&#x4E9B;&#x635F;&#x4F24;&#x540E;&#x7684;&#x86CB;&#x767D;&#x8D28;&#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x3002;

&#x810A;&#x9AD3; NR1 &#x4E1D;&#x6C28;&#x9178;&#x78F7;&#x9178;&#x5316;&#x548C; NR2B &#x4E9A;&#x57FA;&#x6291;&#x5236;&#x540E;&#x5468;&#x56F4;&#x708E;&#x3002;

Spinal cord N-methyl-D-aspartate (NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further examined the level of expression of these proteins following the injury.

Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation.

La moelle &#xE9;pini&#xE8;re N-m&#xE9;thyl-D-aspartate (NMDA) sont intimement impliqu&#xE9;s dans le d&#xE9;veloppement et la maintenance de la sensibilisation centrale. Cependant, les m&#xE9;canismes de m&#xE9;diation de l&#x26;#39;alt&#xE9;ration de la fonction des r&#xE9;cepteurs NMDA ne sont pas bien comprises. Dans cette &#xE9;tude, le r&#xF4;le de la phosphorylation des variants d&#x26;#39;&#xE9;pissage NR1 et sous-unit&#xE9;s NR2 a &#xE9;t&#xE9; examin&#xE9; &#xE0; la suite inflammation de la patte post&#xE9;rieure chez le rat. Nous avons en outre examin&#xE9; le niveau d&#x26;#39;expression de ces prot&#xE9;ines apr&#xE8;s la blessure.

Spinal Cord phosphorylation de la s&#xE9;rine et la r&#xE9;pression NR1 Subunit NR2B Apr&#xE8;s inflammation p&#xE9;riph&#xE9;rique

R&#xFC;ckenmark NR1 Serinphosphorylierung NR2B-Untereinheit und Unterdr&#xFC;ckung nach peripherer Entz&#xFC;ndung.

Recettori N-metil-D-aspartato (NMDA) del midollo spinale sono intimamente coinvolti nello sviluppo e nella manutenzione di sensibilizzazione centrale. Tuttavia, i meccanismi di mediazione l&#39;alterata funzione dei recettori NMDA non sono ben compresi. In questo studio &egrave; stato esaminato il ruolo della fosforilazione delle varianti di splicing NR1 e subunit&agrave; NR2 seguito infiammazione zampa posteriori nei ratti. Abbiamo esaminato ulteriormente il livello di espressione di queste proteine dopo l&#39;infortunio.

Midollo spinale NR1 serina fosforilazione e soppressione di subunit&agrave; NR2B seguendo l&#39;infiammazione periferica.

&#x810A;&#x9AC4;N-&#x30E1;&#x30C1;&#x30EB;-D-&#x30A2;&#x30B9;&#x30D1;&#x30E9;&#x30AE;&#x30F3;&#x9178;&#xFF08;NMDA&#xFF09;&#x53D7;&#x5BB9;&#x4F53;&#x306F;&#x5BC6;&#x63A5;&#x306B;&#x4E2D;&#x67A2;&#x6027;&#x611F;&#x4F5C;&#x306E;&#x958B;&#x767A;&#x3068;&#x4FDD;&#x5B88;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;NMDA&#x53D7;&#x5BB9;&#x4F53;&#x306E;&#x5909;&#x5316;&#x3057;&#x305F;&#x6A5F;&#x80FD;&#x3092;&#x5A92;&#x4ECB;&#x3059;&#x308B;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306F;&#x3088;&#x304F;&#x7406;&#x89E3;&#x3055;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;NR1&#x30B9;&#x30D7;&#x30E9;&#x30A4;&#x30B9;&#x5909;&#x7570;&#x4F53;&#x304A;&#x3088;&#x3073;NR2&#x30B5;&#x30D6;&#x30E6;&#x30CB;&#x30C3;&#x30C8;&#x306E;&#x30EA;&#x30F3;&#x9178;&#x5316;&#x306E;&#x5F79;&#x5272;&#x306F;&#x3001;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x5F8C;&#x8DB3;&#x306E;&#x708E;&#x75C7;&#x5F8C;&#x306B;&#x691C;&#x8A0E;&#x3057;&#x305F;&#x3002;&#x6211;&#x3005;&#x306F;&#x3055;&#x3089;&#x306B;&#x640D;&#x50B7;&#x5F8C;&#x306E;&#x3053;&#x308C;&#x3089;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x767A;&#x73FE;&#x30EC;&#x30D9;&#x30EB;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x305F;&#x3002;

&#x810A;&#x9AC4;NR1&#x306E;&#x30BB;&#x30EA;&#x30F3;&#x306E;&#x30EA;&#x30F3;&#x9178;&#x5316;&#x3068;&#x672B;&#x68A2;&#x306E;&#x708E;&#x75C7;&#x306B;&#x7D9A;&#x3044;&#x3066;NR2B&#x30B5;&#x30D6;&#x30E6;&#x30CB;&#x30C3;&#x30C8;&#x6291;&#x5236;

&#xCC99;&#xC218; N-&#xBA54; &#xD2F8;-D-aspartate (NMDA) &#xC218;&#xC6A9; &#xCCB4; &#xAC1C;&#xBC1C; &#xBC0F; &#xC720;&#xC9C0; &#xBCF4;&#xC218; &#xC911;&#xC559; &#xBBFC;&#xAC10;&#xC131;&#xC5D0; &#xBC00;&#xC811; &#xD558; &#xAC8C; &#xAD00;&#xB828; &#xB429;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, NMDA &#xC218;&#xC6A9; &#xCCB4;&#xC758; &#xBCC0;&#xACBD; &#xB41C; &#xAE30;&#xB2A5;&#xC744; &#xC911;&#xC7AC; &#xD558;&#xB294; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xC798; &#xC774;&#xD574; &#xD558;&#xC9C0;. &#xBCF8;&#xC774; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C;&#xB294; NR1 &#xC2A4;&#xD50C;&#xB77C;&#xC774;&#xC2A4; &#xBCC0;&#xC885;&#xACFC; NR2 subunits&#xC758; &#xC778; &#xC0B0;&#xD654;&#xC758; &#xC5ED;&#xD560; &#xC950;&#xC5D0;&#xC11C; &#xB4B7; &#xBC1C; &#xC5FC;&#xC99D;&#xC5D0; &#xB530;&#xB77C; &#xC870;&#xC0AC; &#xB418;&#xC5C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xB354;&#xC6B1; &#xC2DD; &#xBD80;&#xC0C1;&#xC5D0; &#xB530;&#xB77C; &#xC774;&#xB7EC;&#xD55C; &#xB2E8;&#xBC31;&#xC9C8;&#xC758; &#xC218;&#xC900;&#xC744; &#xC870;&#xC0AC; &#xD588;&#xB2E4;.

&#xCC99;&#xC218; NR1 &#xB5A0;&#xB4E4;&#xACE0; &#xC778; &#xC0B0;&#xD654; &#xBC0F; &#xC8FC;&#xBCC0; &#xC5FC;&#xC99D;&#xC5D0; &#xB530;&#xB77C; NR2B &#xC18C; &#xB2E8;&#xC704; &#xC5B5;&#xC81C;.

Recent work has indicated an increasingly complex role for astrocytes in the central nervous system. Astrocytes are now known to exchange information with neurons at synaptic junctions and to alter the information processing capabilities of the neurons. As an extension of this trend a hypothesis was proposed that astrocytes function to store information. To explore this idea the ion channels in biological membranes were compared to models known as cellular automata. These comparisons were made to test the hypothesis that ion channels in the membranes of astrocytes form a dynamic information storage device.

Memory in astrocytes: a hypothesis.

Travaux r&eacute;cent ont montr&eacute; un r&ocirc;le de plus en plus complex pour les astrocytes du syst&egrave;me nerveux central. Les astrocytes sont maintenant connus pour &eacute;changer des informations avec les neurones au niveau des jonctions synaptiques et d&#39;alt&eacute;rer la capacit&eacute;s des neurones de traitement de l&#39;information. Dans le prolongement de cette tendance, une hypoth&egrave;se a &eacute;t&eacute; propos&eacute;e cette fonction d&#39;astrocytes pour stocker des informations. Pour explorer cette id&eacute;e, les canaux ioniques dans les membranes biologiques ont &eacute;t&eacute; compar&eacute;s aux mod&egrave;les appel&eacute;s automates cellulaires. Ces comparaisons ont &eacute;t&eacute; faites pour v&eacute;rifier l&#39;hypoth&egrave;se que les canaux ioniques dans les membranes des astrocytes forme un dispositif de stockage d&#39;informations dynamiques.

M&eacute;moire dans les astrocytes : une hypoth&egrave;se.

Lavoro recente ha indicato un ruolo sempre pi&ugrave; complesso per gli astrociti del sistema nervoso centrale. Gli astrociti sono ora conosciuti per lo scambio di informazioni con i neuroni a giunzioni sinaptiche e alterare la capacit&agrave; dei neuroni di elaborazione di informazioni. Come un&#39;estensione di questa tendenza un&#39;ipotesi &egrave; stata proposta quella funzione di astrociti per memorizzare le informazioni. Per esplorare questa idea i canali ionici in membrane biologiche sono state rispetto ai modelli conosciuti come gli automi cellulari. Questi confronti sono stati fatti per testare l&#39;ipotesi che i canali ionici nelle membrane degli astrociti formano una periferica di archiviazione di informazioni dinamiche.

Memoria negli astrociti: un&#39;ipotesi.

Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing.

Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin.

Plusieurs chercheurs ont coupl&eacute; des toxines &agrave; neuropeptides dans le but de neurones sp&eacute;cifiques de l&eacute;sion du syst&egrave;me nerveux central. En produisant des d&eacute;ficits en fonction de ces toxines conjugu&eacute;s ont donn&eacute; des informations pr&eacute;cieuses sur le r&ocirc;le de ces cellules. Dans un effort pour sp&eacute;cifiquement stimuler les cellules plut&ocirc;t que de les tuer, nous avons conjugu&eacute; le neuropeptide substance P &agrave; la sous-unit&eacute; catalytique de la toxine chol&eacute;rique (SP-CTA). Ce conjugu&eacute; devrait &ecirc;tre repris de mani&egrave;re s&eacute;lective par r&eacute;cepteur neurokinine exprimant les neurones r&eacute;sultant de l&#39;activit&eacute; accrue de l&#39;ad&eacute;nylate cyclase et d&eacute;charge neuronale.

Sensibilisation des neurones nociceptifs m&eacute;dullaires avec un conjugu&eacute; de la substance P et la toxine chol&eacute;rique.

Diversi ricercatori hanno accoppiato tossine di neuropeptidi ai fini specifici neuroni lesioning nel sistema nervoso centrale. Producendo deficit nella funzione questi coniugati tossina hanno fornito preziose informazioni circa il ruolo di queste cellule. Nel tentativo di specificamente stimolano le cellule piuttosto che ucciderli noi abbiamo coniugato il neuropeptide sostanza P per la subunit&agrave; catalitica della tossina colerica (SP-CTA). Questo coniugato deve essere preso in modo selettivo dal recettore Neurochinina esprimendo i neuroni con conseguente attivit&agrave; avanzata dell&#39;adenilato ciclasi e firing neuronale.

Sensibilizzazione dei neuroni nocicettivo del midollo spinale con un coniugato di sostanza P e tossina colerica.

Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA-injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury.

Central sensitization in the trigeminal nucleus caudalis produced by a conjugate of substance P and the A subunit of cholera toxin.

Personnes souffrant de douleur chronique de craniofaciale &eacute;prouver des sympt&ocirc;mes qui correspondent &agrave; une sensibilisation centrale. En fait, la sensibilisation centrale peut constituer le processus majeur de la maladie dans ces conditions, surtout si la l&eacute;sion initiale est gu&eacute;rie ou la condition est idiopathique. Pour comprendre la sensibilisation centrale, nous avons d&eacute;velopp&eacute; un conjugu&eacute; de la substance P et la toxine chol&eacute;rique (SP-CTA). SP-LTC est s&eacute;lectivement absorb&eacute; par les cellules qui expriment des r&eacute;cepteurs de la neurokinine. Vingt-quatre heures apr&egrave;s l&#39;administration intracisternale de SP-LTC, souris et le rat sauvage fait montre d&#39;arri&egrave;re-plan persistants nociception, mais pour l&#39;essai de sensibilit&eacute; au froid du visage, ils ne diff&egrave;rent pas des contr&ocirc;les. Cependant, traiter les animaux SP-LTC-inject&eacute; avec du naloxone expos&eacute;s une hypersensibilit&eacute; au froid au visage. R&eacute;cepteur MU-opio&iuml;de knockout souris trait&eacute;es avec hypersensibilit&eacute; SP-LTC a d&eacute;montr&eacute; sans traitement de naloxone. Ces r&eacute;sultats sugg&egrave;rent que la sensibilisation centrale conduit &agrave; l&#39;activation d&#39;un syst&egrave;me opio&iuml;de endog&egrave;ne. Les donn&eacute;es montrent &eacute;galement que l&#39;administration intracisternale de SP-LTC chez les rongeurs est un mod&egrave;le utile pour l&#39;&eacute;tude de sensibilisation centrale comme un processus de la maladie sans avoir &agrave; induire une l&eacute;sion p&eacute;riph&eacute;rique.

Sensibilisation centrale dans le noyau du trijumeau caudalis produites par un conjugu&eacute; de la substance P et la sous-unit&eacute; A de la toxine chol&eacute;rique.

Gli individui con dolore craniofacciale cronico sintomi che sono coerenti con una sensibilizzazione centrale. In realt&agrave;, sensibilizzazione centrale pu&ograve; costituire il processo della malattia principale in queste condizioni, specialmente se la lesione originale ha guarito o la condizione &egrave; idiopatica. Per capire la sensibilizzazione centrale abbiamo sviluppato un coniugato della sostanza P e tossina colerica (SP-CTA). SP-CTA &egrave; preso in modo selettivo dalle cellule che esprimono i recettori Neurochinina. Ventiquattro ore dopo la somministrazione di intracisternal di SP-CTA, selvaggio-tipo ratti e topi hanno dimostrato segni di nocicezione sfondo persistente, ma durante il test per la sensibilit&agrave; del viso freddo, non differiscono dai controlli. Tuttavia, nel trattamento degli animali SP-CTA-iniettato con naloxone esposto ipersensibilit&agrave; al freddo in faccia. Topi knockout del recettore mu-oppioide trattati con SP-CTA dimostrato ipersensibilit&agrave; senza trattamento di naloxone. Questi risultati suggeriscono che una sensibilizzazione centrale conduce all&#39;attivazione di un sistema degli oppioidi endogeno. I dati dimostrano anche che l&#39;amministrazione intracisternal di SP-CTA in roditori &egrave; un modello utile per studiare la sensibilizzazione centrale come un processo di malattia senza dover indurre un danno periferico.

Sensibilizzazione centrale al nucleo del trigemino caudalis prodotta da un coniugato della sostanza P e la subunit&agrave; A della tossina colerica.

Detecting behaviors related to orofacial pain in rodent models often relies on subjective investigator grades or methods that place the animal in a stressful environment. In this study, an operant-based behavioral assay is presented for the assessment of orofacial tactile sensitivity in the rat.

A novel operant-based behavioral assay of mechanical allodynia in the orofacial region of rats.

To assess changes in orofacial tactile sensitivity and gnawing related to capsaicin-mediated cutaneous, myogenic, and arthrogenic nociception in the rat.

Robert M. Caudle

Department of Oral and Maxillofacial Surgery

University of Florida College of Dentistry

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay

Robert M. Caudle

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Oral and Maxillofacial Surgery

University of Florida College of Dentistry

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay

Department of Oral and Maxillofacial Surgery