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1.
World Neurosurg ; 188: e561-e566, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825311

RESUMO

BACKGROUND: Spinal anesthesia (SA) is used in lumbar surgery, but initial adequate analgesia fails in some patients. In these cases, spinal redosing or conversion to general endotracheal anesthesia is required, both of which are detrimental to the patient experience and surgical workflow. METHODS: We reviewed cases of lumbar surgery performed under SA from 2017-2021. We identified 12 cases of inadequate first dose and then selected 36 random patients as controls. We used a measurement tool to approximate the volume of the dural sac for each patient using T2-weighted sagittal magnetic resonance imaging sequences. RESULTS: Patients who had an inadequate first dose of anesthesia had a significantly larger dural sac volume, 22.8 ± 7.9 cm3 in the inadequate dose group and 17.4 ± 4.7 cm3 in controls (P = 0.043). The inadequate dose group was significantly younger, 54.2 ± 8.8 years in failed first dose and 66.4 ± 11.9 years in controls (P = 0.001). The groups did not differ by surgical procedure (P = 0.238), level (P = 0.353), American Society of Anesthesia score (P = 0.546), or comorbidities. CONCLUSIONS: We found that age, larger height, and dural sac volume are risk factors for an inadequate first dose of SA. The availability of spinal magnetic resonance imaging in patients undergoing spine surgery allows the preoperative measurement of their thecal sac size. In the future, these data may be used to personalize spinal anesthesia dosing on the basis of individual anatomic variables and potentially reduce the incidence of failed spinal anesthesia in spine surgery.


Assuntos
Raquianestesia , Vértebras Lombares , Humanos , Pessoa de Meia-Idade , Raquianestesia/métodos , Feminino , Masculino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Idoso , Imageamento por Ressonância Magnética , Adulto , Estudos Retrospectivos , Dura-Máter/cirurgia , Dura-Máter/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos
2.
World Neurosurg ; 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37295471

RESUMO

BACKGROUND: Spinal anesthesia is an effective modality for lumbar surgery. Patient eligibility with respect to medical comorbidities remains a topic of debate. Obesity (body mass index ≥30 kg/m2), anxiety, obstructive sleep apnea, reoperation at the same level, and multilevel operations have variously been reported as relative contraindications. We hypothesize that patients undergoing common lumbar surgeries with these comorbidities do not experience greater rates of complications compared with controls. METHODS: We analyzed a prospectively collected database of patients undergoing thoracolumbar surgery under spinal anesthesia and identified 422 cases. Surgeries were less than 3 hours (the duration of action of intrathecal bupivacaine) and include microdiscectomies, laminectomies, and both single-level and multilevel fusions. Procedures were performed by a single surgeon at a single academic center. In overlapping groups, 149 patients had a body mass index ≥30 kg/m2, 95 had diagnosed anxiety, 79 underwent multilevel surgery, 98 had obstructive sleep apnea, and 65 had a previous operation at the same level. The control group included 132 patients who did not have these risk factors. Differences in important perioperative outcomes were assessed. RESULTS: There were no statistically significant differences in intraoperative and postoperative complications except 2 cases of pneumonia in the anxiety group and 1 case in the reoperative group. There were also no significant differences for patients with multiple risk factors. Rates of spinal fusion were similar among groups, although mean length of stay and operative time were different. CONCLUSIONS: Spinal anesthesia is a safe option for patients with significant comorbidities and can be considered for most patients undergoing routine lumbar surgeries.

3.
Oper Neurosurg (Hagerstown) ; 24(3): 283-290, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36701492

RESUMO

BACKGROUND: Spinal anesthesia is safe and effective in lumbar surgeries, with numerous advantages over general anesthesia (GA). Nevertheless, 1 major concern preventing the widespread adoption of this anesthetic modality in spine surgeries is the potential for intraprocedural anesthetic failure, resulting in the need to convert to GA intraoperatively. OBJECTIVE: To present a novel additional prone dose algorithm for when a first spinal dose fails to achieve the necessary effect. METHODS: A total of 422 consecutive patients undergoing simple and complex thoracolumbar surgeries under spinal anesthesia were prospectively enrolled into our database. Data were retrospectively collected through extraction of electronic health records. RESULTS: Sixteen of 422 required a second prone dose, of whom 1 refused and was converted to GA preoperatively. After 15 were given a prone dose, only 2 required preoperative conversion to GA. There were no instances of intraoperative conversion to GA. The success rate for spinal anesthesia without the need for conversion rose from 96.4% to 99.5%. In patients who required a second prone dose, there were no instances of spinal headache, deep vein thrombosis, pneumonia, urinary tract infection, urinary retention, readmission within 30 days, acute pain service consult, return to operating room, durotomy, or cerebrospinal fluid on puncture. CONCLUSION: Use of an additional prone dose algorithm was able to achieve a 99.5% success rate, and those who received this second dose did not experience any complications or negative operative disadvantages. Further research is needed to investigate which patients are at increased risk of inadequate analgesia with spinal anesthesia.


Assuntos
Raquianestesia , Humanos , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Estudos Retrospectivos , Coluna Vertebral , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos
4.
Saudi J Anaesth ; 16(3): 327-331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898523

RESUMO

Postoperative pulmonary complications (PPCs) occur frequently and are associated with a prolonged hospital stay, increased mortality, and high costs. Patients with morbid obesity are at higher risk of perioperative complications, in particular associated with those related to respiratory function. One of the most prominent concerns of the anesthesiologists while taking care of the patient with obesity in the perioperative setting should be the status of the lung and delivery of mechanical ventilation as its strategy affects clinical outcomes. Negative effects of mechanical ventilation on the respiratory system known as ventilator-induced lung injury include barotrauma, volutrauma, and atelectrauma. However, the optimal regimen of mechanical ventilation still remains a matter of debate. While low tidal volume (VT) strategy has become a widely accepted standard of care, the protective role of PEEP and recruitment maneuvers is less clear. This review focuses on the pathophysiology of respiratory function in patients with morbid obesity, the effects of mechanical ventilation on the lungs, and optimal intraoperative strategy based on the current state of knowledge.

5.
Surg Neurol Int ; 13: 42, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242408

RESUMO

BACKGROUND: Spinal anesthesia is being increasingly recognized as a favorable alternative to general anesthesia. However, there are still several considerations for its safe and effective use. CASE DESCRIPTION: A 62-year-old male received spinal anesthesia during an uneventful L3-L5 decompressive laminectomy. However, he subsequently experienced a brief episode of pulseless electrical activity in the post-anesthesia care unit, and was successfully resuscitated without further sequelae. This was attributed to a vasovagal episode, with his notable prior history of experiencing vasovagal syncope with lightheadedness and fainting at the sight of blood. CONCLUSION: Patients with a history of vasovagal syncope may be predisposed to experiencing brief potentiated episodes of severe bradycardia and even cardiac arrest following spinal anesthesia.

6.
Oper Neurosurg (Hagerstown) ; 23(4): 298-303, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36106935

RESUMO

BACKGROUND: Spinal anesthesia is a safe and effective alternative to general anesthesia for patients undergoing lumbar spine surgery, and numerous reports have demonstrated its advantages. To the best of our knowledge, no group has specifically reported on the use of spinal anesthesia in thoracic-level spine surgeries because there is a hypothetical risk of injuring the conus medullaris at these levels. With the advantages of spinal anesthesia and the desire for many elderly patients to avoid general anesthesia, our group has uniquely explored the use of this modality on select patients with thoracic pathology requiring surgical intervention. OBJECTIVE: To investigate the feasibility of performing thoracic-level spinal surgeries under spinal anesthesia and report our experience with 3 patients. METHODS: A retrospective chart review of medical records was undertaken, involving clinical notes, operative notes, and anesthesia records. RESULTS: Three spinal stenosis patients underwent thoracic laminectomy under spinal anesthesia. Two surgeries were performed at the T11-T12 level and 1 at the T12-L1 level. The average age was 82 years, average American Society of Anesthesiologists score was 3.3, and 1 identified as female. Two cases used hyperbaric 0.75% bupivacaine dissolved in dextrose, and 1 used isobaric 0.5% bupivacaine dissolved in water. CONCLUSION: Spinal anesthesia is feasible for thoracic-level spine procedures, even in elderly patients with comorbidities. We describe our cases and technique for safely achieving a thoracic level of analgesia, as well as discuss recommendations, adverse events, and considerations for the use of spinal anesthesia during lower thoracic-level spine operations.


Assuntos
Raquianestesia , Idoso , Idoso de 80 Anos ou mais , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Bupivacaína , Feminino , Glucose , Humanos , Vértebras Lombares/cirurgia , Estudos Retrospectivos
7.
Clin Neurol Neurosurg ; 222: 107454, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36201900

RESUMO

OBJECTIVE: Postoperative urinary retention (POUR) is a common and vexing complication in elective spine surgery. Efficacious prevention strategies are still lacking, and existing studies focus primarily on identifying risk factors. Spinal anesthesia has become an attractive alternative to general anesthesia in elective lumbar surgery, with the potential of having a differential impact on POUR. METHODS: 422 spinal anesthesia procedures were prospectively collected between 2017 and 2021 and compared to 416 general anesthesia procedures retrospectively collected between 2014 and 2017, at a single academic center by the same senior neurosurgeon. The main outcome was POUR, defined as the need for straight bladder catheterization or indwelling bladder catheter placement after surgery due to failure to void. A power calculation was performed prior to data collection. RESULTS: The general anesthesia group had a higher rate of POUR (9.1 %) compared with the spinal anesthesia group (4.3 %), p = 0.005. At baseline, the spinal anesthesia cohort had an older average age and fewer patients with a history of previous spine surgery. Other comorbid conditions were comparable between the groups. For perioperative characteristics, spinal anesthesia patients had higher ASA scores, shorter operative times, shorter lengths of hospital stay, less operative levels, and zero use of intraoperative bladder catheterization. Acute pain service consult was similar between the groups. A multivariable logistic regression revealed that spinal anesthesia was associated with a significantly lower rate of urinary retention in the spinal anesthesia group (p = 0.0130), after adjusting for potentially confounding factors. Other statistically significant risk factors for POUR included diabetes, (p = 0.003), BPH (p = 0.014), operative time (p = 4.94e-06), and ASA score (p = 0.005). CONCLUSIONS: We collect and analyze one of the largest available cohorts of patients undergoing simple and complex surgeries under spinal and general anesthesia, finding that spinal anesthesia is independently associated with a lower incidence of POUR compared to general anesthesia, even when adjusted for potentially confounding risk factors. Further prospective trials are needed to explore this finding.


Assuntos
Raquianestesia , Retenção Urinária , Humanos , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Estudos Retrospectivos , Cateterismo Urinário/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Raquianestesia/efeitos adversos , Anestesia Geral/efeitos adversos , Fatores de Risco
8.
Mayo Clin Proc ; 97(9): 1734-1751, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36058586

RESUMO

Cardiovascular conditions such as hypertension, arrhythmias, and heart failure are common in patients undergoing anesthesia for surgical or other procedures. Numerous guidelines from various specialty societies offer variable recommendations for the perioperative management of these medications. The Society for Perioperative Assessment and Quality Improvement identified a need to provide multidisciplinary evidence-based recommendations for preoperative medication management. The society convened a group of 13 members with expertise in perioperative medicine and training in anesthesiology or internal medicine. The aim of this consensus effort is to provide perioperative clinicians with guidance on the management of cardiovascular medications commonly encountered during the preoperative evaluation. We used a modified Delphi process to establish consensus. Twenty-one classes of medications were identified: α-adrenergic receptor antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, ß-adrenoceptor blockers, calcium-channel blockers, centrally acting sympatholytic medications, direct-acting vasodilators, loop diuretics, thiazide diuretics, potassium-sparing diuretics, endothelin receptor antagonists, cardiac glycosides, nitrodilators, phosphodiesterase-5 inhibitors, class III antiarrhythmic agents, potassium-channel openers, renin inhibitors, class I antiarrhythmic agents, sodium-channel blockers, and sodium glucose cotransportor-2 inhibitors. We provide recommendations for the management of these medications preoperatively.


Assuntos
Hipertensão , Melhoria de Qualidade , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antiarrítmicos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Potássio/uso terapêutico , Sódio , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico
9.
Eur J Surg Oncol ; 46(12): 2311-2323, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32826114

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part II of the guidelines highlights postoperative management and special considerations. METHODS: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations. RESULTS: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items. No consensus could be reached regarding the preemptive use of fresh frozen plasma. CONCLUSION: The present ERAS recommendations for CRS ± HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS ± HIPEC and to prospectively evaluate recommendations in clinical practice.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Recuperação Pós-Cirúrgica Melhorada/normas , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/terapia , Cuidados Pós-Operatórios/normas , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/normas , Técnica Delphi , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/normas , Neoplasias Peritoneais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório
10.
Eur J Surg Oncol ; 46(12): 2292-2310, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32873454

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management. METHODS: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations. RESULTS: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma. CONCLUSION: The present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Recuperação Pós-Cirúrgica Melhorada , Quimioterapia Intraperitoneal Hipertérmica/métodos , Cuidados Intraoperatórios/métodos , Neoplasias Peritoneais/terapia , Cuidados Pré-Operatórios/métodos , Técnica Delphi , Humanos , Assistência Perioperatória
12.
Shock ; 29(6): 656-61, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18091573

RESUMO

There are few blood biomarkers predictive of mortality in adult respiratory distress syndrome (ARDS), and none that currently serve as therapeutic targets. Here, we ask whether a circulating protein angiopoietin 2 (Ang2) correlates with severity of lung injury and mortality in a surgical intensive care unit cohort with acute lung injury (ALI)/ARDS. Tie 2 is a tyrosine kinase receptor expressed on endothelial cells. One ligand, angiopoietin 1, phosphorylates Tie 2 and stabilizes adult vasculature. An alternate ligand, Ang2, serves as a context-dependent antagonist and disrupts barrier function. Previously, our laboratory detected high circulating Ang2 levels in septic patients and a correlation with low Pa(O2)/F(IO2). In this study, daily plasma was collected in 63 surgical intensive care unit patients. Eighteen patients met clinical criteria for ALI or ARDS. The median Ang2 at admission in patients who never developed ALI/ARDS was 3.7 ng/mL (interquartile range [IQR], 5.6; n = 45). The Ang2 on the day a patient met criteria for ALI/ARDS was 5.3 ng/mL (IQR, 6.7) for survivors (n = 11) and 19.8 ng/mL (IQR, 19.2) for nonsurvivors (n = 7; P= 0.004). To explore the mechanism of high Ang 2 leading to increased permeability, plasma from patients with ALI was applied to cultured lung endothelial cells and found to disrupt normal junctional architecture. This effect can be rescued with the Tie 2 agonist angiopoietin 1. A patient's convalescent (low Ang2) plasma did not disrupt junctional architecture. Although further studies with larger sample sizes will be needed to confirm these results, high Ang2 in critically ill patients with ALI/ARDS is associated with a poor outcome. These data, coupled with our cell culture experiments, suggest that antagonism of Ang2 may provide a future novel therapeutic target for ARDS.


Assuntos
Angiopoietina-2/sangue , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/mortalidade , Idoso , Angiopoietina-1/sangue , Biomarcadores/sangue , Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Valor Preditivo dos Testes , Receptor TIE-2/metabolismo , Síndrome do Desconforto Respiratório/cirurgia
13.
Intensive Care Med ; 33(6): 1050-4, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17393138

RESUMO

OBJECTIVE: We developed a novel pressure transducer-based method of continuous measurement of head of bed elevation. Following validation of the method we hypothesized that head of bed angles would be at or above 30 degrees among mechanically ventilated patients throughout the day due to a hospital-wide initiative on ventilator-associated pneumonia prevention and standardized electronic order entry system to keep head of bed at an angle of 30 degrees or greater. DESIGN AND SETTING: Prospective observational study in university hospital intensive care units. PATIENTS AND PARTICIPANTS: Twenty-nine consecutive mechanically ventilated patients with no contraindications for semirecumbency. MEASUREMENTS AND RESULTS: We acquired 113 pairs of measurements on unused beds for validation of the method at angles between 3 degrees and 70 degrees. Correlation between transducer and protractor was fitted into a linear regression model (R2 = 0.98) with minimal variation of data along the line of equality. Bland-Altman analysis showed a mean difference of 1.6 degrees +/- 1.6 degrees. Ninety-six percent of differences were within 2 SD from the mean. This method was then used among 29 intubated patients to collect head of bed data over a 24-h period for 3 consecutive days. Contrary to our hypothesis, all patients had head of bed angles less than 30 degrees. CONCLUSIONS: Our results suggest that this method could be used with high reliability and patients in our institution were not kept even at 30 degrees. The results are in accord with those of a recent study which found that continued maintenance of previously suggested head of bed angles was difficult to attain clinically. This may lead us to reevaluate methods studying the impact of head of bed elevation in VAP prevention.


Assuntos
Leitos , Desenho de Equipamento , Respiração Artificial , Decúbito Dorsal , Cuidados Críticos , Hospitais Urbanos , Humanos , Unidades de Terapia Intensiva , Massachusetts , Monitorização Fisiológica , Pneumonia Associada à Ventilação Mecânica/prevenção & controle
14.
A A Case Rep ; 8(8): 192-196, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28151764

RESUMO

Most modern anesthesia workstations provide automated checkout, which indicates the readiness of the anesthesia machine. In this case report, an anesthesia machine passed the automated machine checkout. Minutes after the induction of general anesthesia, we observed a mismatch between the selected and delivered tidal volumes in the volume auto flow mode with increased inspiratory resistance during manual ventilation. Endotracheal tube kinking, circuit obstruction, leaks, and patient-related factors were ruled out. Further investigation revealed a broken internal insert within the CO2 absorbent canister that allowed absorbent granules to cause a partial obstruction to inspiratory and expiratory flow triggering contradictory alarms. We concluded that even when the automated machine checkout indicates machine readiness, unforeseen equipment failure due to unexpected events can occur and require providers to remain vigilant.


Assuntos
Anestesia com Circuito Fechado/instrumentação , Monitorização Intraoperatória/métodos , Respiração Artificial/instrumentação , Automação , Alarmes Clínicos , Desenho de Equipamento , Falha de Equipamento , Segurança de Equipamentos , Humanos , Segurança do Paciente
15.
Exp Biol Med (Maywood) ; 231(6): 1165-70, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16741070

RESUMO

Subcutaneous endothelin-1 (ET-1; 200 microM, 2 nmoles/paw) injected into the rat hind paw, has been shown to cause robust hind paw flinching (HPF) and paw licking, and to induce impulses selectively in primary nociceptors. Here we report that a much lower [ET-1] sensitizes the paw to a nocifensive withdrawal response to tactile stimulation (by von Frey hairs, VFH), a sensitization that involves local TRPV1 receptors. Injection of 10 microM ET-1 (0.1 nmole/paw) causes only marginal HPF but rapidly (20 mins after injection) lowers the force threshold for paw withdrawal (PWT) to VFH, to approximately 30% of pre-injection baseline. Such tactile allodynia persists for 3 hrs. In rats pre-injected with the TRPV1-antagonists capsazepine (CPZ; 1.33 mM) or 5'-iodoresiniferatoxin (I-RTX; 0.13 microM), 15 min before ET-1, a fast initial drop in PWT, as with ET-1 alone, occurs (to 40% or to 19% of baseline, respectively), but this earliest reduction then regresses back to the pre-injection PWT value more rapidly than with ET-1 alone. The recovery of allodynia from the maximum value is about two times faster for ET-1+CPZ and about 4 times faster for ET-1+ I-RTX, compared with that from ET-1 +vehicle (t(1/2) = 130, 60, and 250 mins, respectively). In contrast, spontaneous pain indicated by overt HPF from ET-1 is not attenuated by TRPV1 antagonists. Tactile allodynia is similarly abbreviated by antagonists of both ET(A) (BQ-123, 32 nmoles/paw) and ET(B) (BQ-788, 30 nmoles/paw) receptors, whereas HPF is abolished by this ET(A) antagonist but enhanced by the ET(B) antagonist. We conclude that low ET-1 causes tactile allodynia, which is characterized by a different time-course and pharmacology than ET-1-induced nociception, and that local TRPV1 receptors are involved in the maintenance of this ET-1-induced allodynia but not in the overt algesic action of ET-1.


Assuntos
Endotelina-1/farmacologia , Dor/induzido quimicamente , Canais de Cátion TRPV/metabolismo , Tato/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Diterpenos/farmacologia , Relação Dose-Resposta a Droga , Endotelina-1/administração & dosagem , Injeções Subcutâneas , Masculino , Nociceptores/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Receptor de Endotelina A/efeitos dos fármacos , Receptor de Endotelina A/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores
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