RESUMO
Background: The popularity of tortoises kept in captivity is increasing and has caused concern regarding the necessity to establish safe and straightforward anaesthesia for those reptiles. Aim: This study aimed to compare four protocols using levobupivacaine in spinal anaesthesia for the blockade of the caudal neuraxis of red-footed tortoises (Chelonoidis carbonarius). Methods: Twenty-four tortoises were randomly assigned into four groups: G1, levobupivacaine 0.75% (1.15 mg kg-1); G2, levobupivacaine 0.37% (1.15 mg kg-1); G3, levobupivacaine 0.75% (2.3 mg kg-1); and G4, levobupivacaine 0.75% (0.1 ml 5 cm-1 of straight carapace length). Tortoises were evaluated for respiratory rate, muscle relaxation, response to hindlimb or tail pinch, and cloacal reflex. Results: A 1.15 mg kg-1 dose of levobupivacaine 0.37% appears adequate for shorter procedures, whereas a 1.15 mg kg-1 dose of levobupivacaine 0.75% should be appropriate for longer procedures in red-footed tortoises. Conclusion: Our results are the first to show the effects of levobupivacaine on spinal anaesthesia in reptiles. Weight-based doses presented more intense and more homogeneous effects than carapace length-based doses in red-footed tortoises. Spinal anaesthesia of red-footed tortoises was safe and effective with any of the weight-based protocols.
Assuntos
Raquianestesia , Anestésicos Locais , Levobupivacaína , Tartarugas , Animais , Levobupivacaína/administração & dosagem , Levobupivacaína/farmacologia , Raquianestesia/veterinária , Raquianestesia/métodos , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Masculino , FemininoRESUMO
Objective: The purpose of this study was to demonstrate heat transfer within oral soft tissues using different lasers under the effect of local anesthetics (LA). Methods: Bovine tongue slices were placed in between two glass slides and at a distance from a thermographic camera. In total, 2-cm-long 240 incisions were made along the surface of the tissue parallel to glass slides and the camera capture field. Incisions were performed using 445-nm and infrared (IR) lasers (970 nm and 980 nm on a continuous wave at 2 W) with 320 µm-initiated (concentrated energy at the tip provided by a blue articulated paper and laser irradiation) and noninitiated (defused energy) fiber (30-sec irradiation period). LA was injected into the specimens before irradiation. The temperature changes in °C (ΔT) and vertical and lateral heat transfer (in mm) were recorded at 10-sec intervals for 30 sec, using thermographic images. The amount of lateral and vertical heat transfer was measured. A repeated analysis of variance statistical comparison test was used to analyze differences between the lateral (width) and the vertical (height) heat transfer for initiated and noninitiated lasers and different lasers. Results: The maximum ΔT in °C utilizing initiated tips of 970, 980, or 445 nm were 11.82 ± 3.46, 7.66 ± 3.24, and 18.94 ± 7.01 and using noninitiated tips were 8.27 ± 1.69, 8.87 ± 2.40, and 12.31 ± 8.65, respectively. Heat transfers (height/width) for initiated were 40.65 ± 10.40/90.65 ± 10.77 mm, 41.50 ± 11.83/83.95 ± 11.20 mm, and 33.70 ± 9.10/95.10 ± 11.17 mm and for noninitiated lasers were 52.95 ± 6.89/96.10 ± 11.17 mm, 47.75 ± 7.41/93.75 ± 14.96 mm, and 31.35 ± 11.40/75.20 ± 19.68 mm, respectively. A statistically significant difference was found between all lasers (p < 0.05) for initiated and noninitiated lasers (except for 970/980 nm for noninitiated lasers). Lower penetration depth (p < 0.05) at 445-nm diode and greater lateral heat spreading (p < 0.05) were identified under LA especially utilizing noninitiated tips without significant difference in IR lasers. Conclusions: LA might negatively influence soft tissues creating scattering when noninitiated tips are used and IR diode laser technology.
Assuntos
Anestésicos Locais , Lasers Semicondutores , Animais , Bovinos , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Língua/efeitos da radiação , Termografia , Temperatura AltaRESUMO
RATIONALE: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. METHODS: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. RESULTS: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K a = 1.89×107 M-1) and decamethonium (K a = 1.01×107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. CONCLUSION: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.
Assuntos
Antídotos , Tetracaína , Animais , Tetracaína/farmacologia , Tetracaína/química , Camundongos , Antídotos/farmacologia , Antídotos/química , Amidas/química , Amidas/farmacologia , Masculino , Anestésicos Locais/farmacologia , Anestésicos Locais/química , Humanos , Bloqueadores Neuromusculares/química , Bloqueadores Neuromusculares/farmacologiaRESUMO
Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.
Assuntos
Anestésicos Locais , Ácido Desoxicólico , Hidrogéis , Ropivacaina , Ropivacaina/química , Ropivacaina/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Ácido Desoxicólico/química , Camundongos , Anestésicos Locais/química , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Analgesia/métodos , Masculino , Peso MolecularRESUMO
Fentanyl combined with bupivacaine in subarachnoid anesthesia exerts a strong synergistic analgesic effect, extending the duration of analgesia. However, the mechanism of enhanced analgesic effect of fentanyl remains elusive. The present study investigated the potential mechanism of the analgesic effect of fentanyl when combined with bupivacaine. The subarachnoid injection (SI) rat model was employed, and SI of fentanyl or/and bupivacaine was used to investigate their analgesic effect. Dorsal root ganglion (DRG)' RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to evaluate the downstream mechanisms of MicroRNAs (miRNAs). Further validation tests included RT-PCR, Western blot, and immunofluorescence. A single SI of fentanyl or bupivacaine decreased the positive responses to stimulation when used alone or in combination. RNA-seq results revealed that miR-381-3p played a role in the fentanyl-driven promotion of analgesia. Bioinformatics analysis and dual-luciferase reporter identified TRPM7 as a direct downstream target gene of miR-381-3p. In vitro, overexpression of miR-381-3p could further block fentanyl-induced expression of TRPM7, p-ERK1/2, CGRP, and SP. In addition, antagomir-381-3p reversed the inhibitory effect of fentanyl on the expression of TRPM7, p-ERK1/2, CGRP, and SP, in vivo; however, TRPM7 siRNA rescued the effect of antagomir-381-3p. In conclusion, fentanyl inhibits p-ERK by targeting TRPM7 via miR-381-3p, lowering the production of CGRP and SP, and ultimately inducing analgesic effects.
Assuntos
Bupivacaína , Fentanila , Gânglios Espinais , MicroRNAs , Canais de Cátion TRPM , Animais , Masculino , Ratos , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Bupivacaína/farmacologia , Sinergismo Farmacológico , Fentanila/administração & dosagem , Fentanila/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Injeções Espinhais , MicroRNAs/genética , Ratos Sprague-Dawley , Canais de Cátion TRPM/genéticaRESUMO
This study aimed to investigate the effects of the intravenous administration of lidocaine in the auditory cortex after the systemic administration of salicylate. Healthy male albino Hartley guinea pigs were divided into two groups. The control group received only lidocaine, whereas the experimental group received lidocaine after checking for the effects of salicylate. Extracellular recordings of spikes in the primary auditory cortex and dorsocaudal areas in healthy albino Hartley guinea pigs were continuously documented (pre- and post-lidocaine, pre- and post-salicylate, and post-salicylate after adding lidocaine to post-salicylate). We recorded 160 single units in the primary auditory cortex from five guinea pigs and 155 single units in the dorsocaudal area from another five guinea pigs to confirm the effects of lidocaine on untreated animals. No significant change was detected in either the threshold or Q10dB value after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Spontaneous firing activity significantly decreased after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Next, we recorded 160 single units in the primary auditory cortex from five guinea pigs and 137 single units in the dorsocaudal area from another five guinea pigs to determine the effects of lidocaine on salicylate-treated animals. The threshold was significantly elevated after salicylate administration; however, no additional change was detected after adding lidocaine to the primary auditory cortex and dorsocaudal areas. Regarding the Q10dB value, lidocaine negated the significant changes induced by salicylate in the primary auditory cortex and dorsocaudal areas. Moreover, lidocaine negated the significant changes in spontaneous firing activities induced by salicylate in the primary auditory cortex and dorsocaudal areas. In conclusion, changes in the Q10dB value and spontaneous firing activities induced by salicylate administration are abolished by lidocaine administration, suggesting that these changes are related to the presence of tinnitus.
Assuntos
Córtex Auditivo , Lidocaína , Salicilatos , Zumbido , Animais , Cobaias , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/fisiopatologia , Lidocaína/farmacologia , Zumbido/induzido quimicamente , Masculino , Salicilatos/farmacologia , Anestésicos Locais/farmacologiaRESUMO
Objective: To determine with mechanical nociceptive threshold (MNT) testing whether distal limb skin sensation is affected by intra-articular anesthesia of the tarsometatarsal joint (TMTJ). Animals and procedure: This was a prospective cohort study. Ten client-owned horses that had intra-articular TMTJ anesthesia were included in the study. The MNT was measured at 6 sites on the distal limb at 3 time points: before anesthesia (T0) and at 10 min (T10) and 30 min (T30) post-injection. Linear mixed-model analyses were done, with the significance level set at P < 0.05. Results: There was an increase in MNT (P = 0.001) across combined testing points between T0 and T30, indicating loss of skin sensation in the distal limb 30 min after TMTJ anesthesia. Regarding individual MNT sites, there were increases at the lateral proximal sesamoid bone (P = 0.002) and dorsal coronary band (P = 0.037) at T30 compared to T0. Conclusion: Intra-articular anesthesia of the TMTJ significantly increased the combined MNT of the skin of the distal limb at 30 min, indicating decreased skin sensation. Clinical relevance: Diagnostic anesthesia of the distal hind limb should be performed before TMTJ block. However, if patient compliance prevents this, lameness evaluation 10 min after blocking may enhance the reliability of interpretation.
Effets de l'anesthésie intra-articulaire de l'articulation tarsométatarsienne sur la sensation cutanée du membre distal chez le cheval. Objectif: Déterminer à l'aide d'un test de seuil nociceptif mécanique (MNT) si la sensation cutanée du membre distal est affectée par l'anesthésie intra-articulaire de l'articulation tarsométatarsienne (ATMT). Animaux et procédure: Il s'agissait d'une étude de cohorte prospective. Dix chevaux appartenant à des clients et ayant subi une anesthésie intra-articulaire pour l'ATMT ont été inclus dans l'étude. Le MNT a été mesuré sur 6 sites du membre distal à 3 moments: avant l'anesthésie (T0) et à 10 min (T10) et 30 min (T30) après l'injection. Des analyses linéaires sur modèles mixtes ont été effectuées, avec le niveau de signification fixé à P < 0,05. Résultats: Il y avait une augmentation du MNT (P = 0,001) sur tous les points de test combinés entre T0 et T30, indiquant une perte de sensation cutanée dans le membre distal 30 minutes après l'anesthésie du ATMT. En ce qui concerne les sites MNT individuels, il y avait des augmentations au niveau de l'os sésamoïde proximal latéral (P = 0,002) et de la bande coronaire dorsale (P = 0,037) à T30 par rapport à T0. Conclusion: L'anesthésie intra-articulaire du ATMT a augmenté de manière significative le MNT combiné de la peau du membre distal à 30 min, indiquant une diminution de la sensation cutanée. Pertinence clinique: Une anesthésie diagnostique du membre postérieur distal doit être réalisée avant le bloc de l'ATMT. Cependant, si l'observance du patient l'empêche, l'évaluation de la boiterie 10 minutes après le blocage peut améliorer la fiabilité de l'interprétation.(Traduit par Dr Serge Messier).
Assuntos
Anestésicos Locais , Animais , Cavalos/fisiologia , Feminino , Masculino , Estudos Prospectivos , Injeções Intra-Articulares/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Membro Posterior , Estudos de Coortes , PeleRESUMO
OBJECTIVE: To investigate the effect of intranasal (IN) flunixin meglumine (FM) and intra-inguinal (IG) lidocaine on castration inflammation using prostaglandin E2 (PGE2) concentration as a biomarker. METHODS: This randomized controlled trial was conducted in March 2022. Blood was collected at -24, 1, and 24 hours postcastration for PGE2 quantification from 195 piglets that received 1 of 8 treatments: (1) saline (1.5 mL) applied IG and IN (0.2 mL) followed by surgical castration (n = 24); (2) saline (1.5 mL) IG and IN (0.2 mL) followed by sham castration (25); (3) lidocaine (20 mg/kg or 1.5 mL) IG followed by surgical castration (24); (4) lidocaine (20 mg/kg or 1.5 mL) IG followed by sham castration (25); (5) FM (2.2 mg/kg) IN followed by surgical castration (25); (6) FM (2.2 mg/kg) IN followed by sham castration (24); (7) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by surgical castration (24); and (8) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by sham castration (24). RESULTS: Prostaglandin E2 concentrations did not increase following the castration procedure and were not an effective biomarker of castration inflammation. Piglets that received lidocaine demonstrated no difference in PGE2 levels across all time points. Piglets administered FM had lower PGE2 concentrations at 1 hour and 20 minutes postdrug administration in both the sham and castrated piglets. CONCLUSIONS: Prostaglandin E2 was not an effective biomarker to quantify castration inflammation. Flunixin meglumine was able to reduce PGE2 concentration in piglets regardless of castration procedure, but lidocaine had no impact. Decreased PGE2 levels in FM-treated pigs are likely associated with the drug's ability to mitigate a noncastration-associated inflammatory process occurring independent of the castration procedure. CLINICAL RELEVANCE: Flunixin meglumine reduced circulating PGE2 concentration in the blood, regardless of the castration procedure, indicating a potential for the drug to mitigate an inflammatory process unrelated to castration.
Assuntos
Biomarcadores , Clonixina , Dinoprostona , Inflamação , Lidocaína , Orquiectomia , Doenças dos Suínos , Animais , Dinoprostona/sangue , Clonixina/análogos & derivados , Clonixina/uso terapêutico , Orquiectomia/veterinária , Masculino , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Lidocaína/farmacologia , Suínos , Biomarcadores/sangue , Inflamação/veterinária , Inflamação/tratamento farmacológico , Doenças dos Suínos/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Anestésicos Locais/farmacologiaRESUMO
OBJECTIVE: To evaluate the in vivo spread of iodinated contrast following injections in the transversus abdominis plane (TAP) and rectus sheath in anesthetized dogs via computed tomography. Secondarily, the time of performing each block was compared. ANIMALS: 6 adult, purpose-bred Beagles. METHODS: In a prospective crossover study, dogs were administered injections either in the rectus sheath or transversus abdominis fascial plane in the same manner as a rectus sheath block (RSB) or TAP block using dilute iodinated contrast. Computed tomography scans were performed immediately following injection (time [T]-0) and at 3, 9, 18, and 30 minutes postinjection. Data regarding the spread in the cranial-caudal and lateral directions and time to perform the injections were compared between the 2 techniques using paired or 2-sample t tests. RESULTS: There was significantly greater spread in the cranial-caudal direction in the RSB group (62.9 ± 6.4 mm vs 54.8 ± 6.8 mm at T30; P = .009), whereas spread in the lateral direction was greater in the TAP group (37.3 ± 3.0 mm vs 48.6 ± 6.1 mm at T30; P < .0001). The RSB injection was performed in a more time-efficient manner than TAP injection (48.2 ± 3.2 seconds vs 82.3 ± 8.7 seconds; P = .03). CONCLUSIONS: In living subjects, RSB injections resulted in greater cranial-caudal spread while TAP injections resulted in greater lateral spread. Rectus sheath block injections were performed in a more time efficient manner compared to a single point TAP injection in anesthetized dogs. CLINICAL RELEVANCE: The RSB was performed in a more time-efficient manner and would likely result in greater coverage of the ventral midline. The TAP block would likely result in more significant regional anesthetic coverage of the lateral abdominal wall. Further studies are required to determine the degree of the clinical significance of these results.
Assuntos
Estudos Cross-Over , Bloqueio Nervoso , Tomografia Computadorizada por Raios X , Animais , Cães , Bloqueio Nervoso/veterinária , Bloqueio Nervoso/métodos , Tomografia Computadorizada por Raios X/veterinária , Estudos Prospectivos , Masculino , Feminino , Músculos Abdominais/diagnóstico por imagem , Músculos Abdominais/inervação , Reto do Abdome/inervação , Reto do Abdome/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologiaRESUMO
The study aimed to compare the quality of perioperative analgesia, the motor block duration, and the effects on main cardiovascular parameters of dexmedetomidine (1 µg/kg/nerve block) or magnesium sulphate (2 mg/kg/nerve block) as adjuvants to 0.3% ropivacaine for sciatic and saphenous nerves block in dogs undergoing tibial plateau leveling osteotomy (TPLO). Dogs randomly received perineural dexmedetomidine-ropivacaine (D group), magnesium sulphate-ropivacaine (M group), or ropivacaine (C group). Fentanyl was administered in case of intraoperative nociception. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale (SF-GCMPS) and VAS scale. The duration of motor blockade and intra- and postoperative cardiovascular parameters were also recorded. Group M required significantly more fentanyl than D group (p = 0.04). Group M had a significantly higher SF-GCMPS score than group C at 4 (p = 0.002) and 5 h after extubation (p = 0.01), and a significantly higher VAS score than group D at 3 h after extubation (p = 0.03), and at 4 h if compared to group C (p = 0.009). No significant differences regarding the duration of motor blockade were detected between groups (p = 0.07). The heart rate was significantly lower in group D than in M and C groups intraoperatively and during the first 1.5 h post extubation. The addition of dexmedetomidine or magnesium sulphate as adjuvants to perineural ropivacaine did not improve the quality of perioperative analgesia and did not prolong the motor blockade in dogs undergoing sciatic and saphenous nerves block for TPLO surgery.
Assuntos
Dexmedetomidina , Sulfato de Magnésio , Bloqueio Nervoso , Osteotomia , Dor Pós-Operatória , Ropivacaina , Animais , Cães , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Ropivacaina/administração & dosagem , Ropivacaina/farmacologia , Sulfato de Magnésio/farmacologia , Sulfato de Magnésio/administração & dosagem , Osteotomia/veterinária , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Masculino , Feminino , Bloqueio Nervoso/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Tíbia/cirurgiaRESUMO
Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.
Assuntos
Anestésicos Locais , Dor Crônica , Lidocaína , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dor Crônica/tratamento farmacológico , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Infusões IntravenosasRESUMO
BACKGROUND: Post-traumatic distal limb wounds cause discomfort and heal gradually by second intention. The topical application of Tri-Solfen (lidocaine hydrochloride, bupivacaine hydrochloride, adrenaline acid tartrate and cetrimide [LBAC]) produces effective postsurgical cutaneous analgesia in lambs, calves and piglets; however, its effect on wounds in horses is unknown. METHODS: The antinociceptive effect, measured by mechanical threshold (MT), and the wound healing impacts of LBAC compared with saline were investigated on surgically created 20 × 20 mm distal limb wounds in 10 horses. Treatment was applied once daily for 7 days following wounding on day 0. Mechanical thresholds were measured after treatment on days 1, 2 and 3. Healing was observed for 25 days. RESULTS: The topical application of LBAC immediately following wounding and its reapplication 24 hours later increased the average MT on the first post-traumatic day by 3 Newtons. However, no antinociceptive benefit was observed on days 2 or 3. Treatment with LBAC did not adversely affect wound healing when compared with saline. LIMITATIONS: Methodological differences preclude absolute MT comparisons between studies. The experimental design did not include a model of contaminated or naturally occurring wounds. CONCLUSION: LBAC may provide an early antinociceptive benefit when applied to uncontaminated surgically created wounds without compromising healing.
Assuntos
Bupivacaína , Epinefrina , Lidocaína , Cicatrização , Animais , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Lidocaína/farmacologia , Cicatrização/efeitos dos fármacos , Cavalos , Epinefrina/administração & dosagem , Bupivacaína/administração & dosagem , Masculino , Cetrimônio , Administração Tópica , Feminino , Analgésicos/uso terapêutico , Analgésicos/administração & dosagem , Resultado do Tratamento , Ferimentos e Lesões/veterinária , Ferimentos e Lesões/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Anestésicos Locais/farmacologia , Pele/lesões , Pele/efeitos dos fármacos , Combinação de MedicamentosRESUMO
CONTEXT: For successfully managing pediatric dental patients, local anesthesia is essential to eliminate pain during or after the operative period. An early recovery from soft-tissue anesthesia after an inferior alveolar nerve block (IANB) should benefit a young child patient by avoiding the risk of inadvertently biting the soft tissues. AIMS: Hence, the purpose of the study was to (1) evaluate and compare the efficacy of pre- and postoperative ibuprofen on pain perception in children who undergo IANB anesthesia with or without the use of PM and (2) evaluate the average time required for reversal of anesthesia symptoms using phentolamine mesylate. METHODS: The present study was a randomized, clinical trial performed among 60 children between 6 and 8 years of age using a convenient sampling method. The children were randomly assigned into four equal groups of 15 each using the computer-generated randomization sequence. IANB anesthesia was performed using 2% lignocaine with 1:100,000 epinephrine, and a mandibular primary molar pulpotomy was performed on each group. Group 1: the ibuprofen tablet was taken 1 h before the onset of the procedure. Group 2: ibuprofen tablet 30 min after the pulpotomy procedure. Group 3: the ibuprofen tablet was taken 1 h before the onset of the procedure, and the Phentolamine mesylate (PM) injection was administered. Group 4: immediately after the pulpotomy, the PM injection was administered, and an ibuprofen tablet was taken 30 min after the pulpotomy procedure. All children were assessed for the duration of soft-tissue anesthesia, their behavior scores and pain rating, as well as the incidence of postoperative self-inflicted injuries. STATISTICAL ANALYSIS USED: A one-way ANOVA was used to compare the average time needed for the reversal of anesthetic symptoms between groups. The effects of phentolamine, local anesthetics, and ibuprofen on the child's behavior and pain scores were compared using the Student's t-test. For the study, P < 0.05 was accepted as statistically significant. RESULTS: The time needed for the full reversal of anesthetic symptoms to manifest on the tongue and lip was substantially reduced by the injection of phentolamine (P < 0.001). The use of phentolamine for reversal or the intake of ibuprofen pre- or postoperatively did not exhibit any significant variation in the behavior, pain experience, or incidence of self-inflicted injuries in the child. CONCLUSION: It is evident that although phentolamine injections shorten the duration of anesthesia, the adjunctive use of pre- or postoperative ibuprofen did not significantly alter pain scores.
Assuntos
Anestesia Dentária , Anestésicos Locais , Ibuprofeno , Nervo Mandibular , Bloqueio Nervoso , Fentolamina , Humanos , Fentolamina/farmacologia , Criança , Bloqueio Nervoso/métodos , Anestesia Dentária/métodos , Feminino , Masculino , Nervo Mandibular/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Percepção da Dor/efeitos dos fármacos , Dor Pós-Operatória/prevenção & controle , Pulpotomia/métodos , Lidocaína/farmacologia , Lidocaína/administração & dosagem , Analgésicos não Narcóticos/uso terapêutico , Analgésicos não Narcóticos/farmacologia , Medição da DorRESUMO
The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Nav1.4 and Nav1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.
Assuntos
Anestésicos Locais , Antiarrítmicos , Simulação de Acoplamento Molecular , Piperidinas , Animais , Antiarrítmicos/farmacologia , Anestésicos Locais/farmacologia , Piperidinas/farmacologia , Piperidinas/química , Ratos , Masculino , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Relação Estrutura-Atividade , Ratos Wistar , Modelos Animais de DoençasRESUMO
Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.
Assuntos
Anestésicos Locais , Benzocaína , Portadores de Fármacos , Lipídeos , Benzocaína/administração & dosagem , Benzocaína/química , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Anestésicos Locais/farmacocinética , Anestésicos Locais/farmacologia , Portadores de Fármacos/química , Animais , Lipídeos/química , Camundongos , Nanoestruturas/química , Liberação Controlada de Fármacos , Masculino , Nanopartículas/químicaRESUMO
BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) is a key enzyme in the sulfation process and is associated with the development and metastasis of various tumors. This study aimed to explore the mechanism by which bupivacaine inhibits melanoma proliferation and metastasis by targeting PAPSS2. METHODS: The effects of bupivacaine on the proliferation of A375 and A2058 melanoma cells were evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labeling, and clonogenic assays. Cell migration, invasion, and PAPSS2 expression were evaluated using Transwell experiments and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. Additionally, an in vivo melanoma tumor model in nude mice was constructed to evaluate the impact of bupivacaine on melanoma growth and metastasis. Immunohistochemistry was used to assess tumor metastasis and PAPSS2 expression levels in the nude mouse model. RESULTS: Experimental results demonstrated that bupivacaine significantly inhibited melanoma proliferation and invasion compared to the control group. Notably, this inhibitory effect was partially reversed by PAPSS2 overexpression. In vivo experiments demonstrated that bupivacaine-treated nude mice exhibited reduced tumor volumes, weights, and fewer lung metastatic foci. Molecular analysis via qRT-PCR and immunohistochemistry analysis further indicated that bupivacaine significantly reduced PAPSS2 in tumor tissues. CONCLUSION: This study confirms that bupivacaine, a local anesthetic, can inhibit melanoma proliferation and metastasis by targeting the PAPSS2 signaling pathway. These findings suggest its potential as an anti-tumor medication and present new treatment strategies for melanoma.
Assuntos
Anestésicos Locais , Bupivacaína , Proliferação de Células , Melanoma , Camundongos Nus , Animais , Humanos , Proliferação de Células/efeitos dos fármacos , Melanoma/patologia , Melanoma/tratamento farmacológico , Bupivacaína/farmacologia , Camundongos , Linhagem Celular Tumoral , Anestésicos Locais/farmacologia , Metástase Neoplásica , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Failure of sub-arachnoid block (SAB), due to resistance to bupivacaine after a recent scorpion sting can lead to multiple block attempts and subsequent conversion to general anaesthesia. We report this case series of 10 patients with successful SAB with newly launched 0.75% hyperbaric ropivacaine, in patients with recent scorpion sting. Thus, intrathecal hyperbaric ropivacaine may be considered as the local anaesthetic agent of choice in patients with scorpion sting to prevent failure of SAB.
Assuntos
Anestésicos Locais , Ropivacaina , Picadas de Escorpião , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amidas/uso terapêutico , Amidas/farmacologia , Amidas/administração & dosagem , Anestésicos Locais/uso terapêutico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Bloqueio Nervoso/métodos , Ropivacaina/uso terapêutico , Ropivacaina/administração & dosagem , Ropivacaina/farmacologia , Picadas de Escorpião/tratamento farmacológico , Picadas de Escorpião/complicações , EscorpiõesRESUMO
OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).
Assuntos
Analgésicos Opioides , Dexmedetomidina , Gastrectomia , Lidocaína , Dor Pós-Operatória , Remifentanil , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Analgésicos Opioides/administração & dosagem , Idoso , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Remifentanil/farmacologia , Laparoscopia , Catastrofização , Adulto , Limiar da Dor/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologiaRESUMO
BACKGROUND: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachyarrhythmias and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction. METHODS: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Approximately, six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (Smax) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation. RESULTS: TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility, although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity. CONCLUSIONS: TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in Smax, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.
Assuntos
Infarto do Miocárdio , Taquicardia Ventricular , Animais , Infarto do Miocárdio/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/etiologia , Suínos , Lidocaína/farmacologia , Anestesia Epidural/métodos , Barorreflexo/efeitos dos fármacos , Período Refratário Eletrofisiológico/efeitos dos fármacos , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Anestésicos Locais/farmacologia , Função Ventricular Direita/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Feminino , Vértebras Torácicas , Sus scrofa , Contração Miocárdica/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Local anaesthetics (LAs) can have detrimental effects on rat, bovine, canine, and human tendon tissues and cells. Currently, there has been no available data on the impact of these drugs on equine tenocytes. Even if LA injection for managing painful tendon conditions in horses is limited, it is usually used via intra-articular, intrasynovial, perineural, and intrathecal as well as for lameness examinations. In this in vitro study, the cytotoxic effects of LAs, including lidocaine, mepivacaine, and bupivacaine on equine tenocytes, in the presence and absence of platelet rich plasma (PRP), were investigated. PRP accelerates tissue healing and can exert cytoprotective effects on different cell types exposed to different stressful conditions, including drugs. Results indicated that the exposure to LAs significantly reduced tenocytes viability in dose- and time-dependent manners while PRP was able to counteract their cytotoxic effects. Furthermore, microscopy and flow cytometry analyses revealed apoptosis and necrosis in equine tenocytes exposed to these drugs, that were both reduced when PRP was in the medium. These findings highlight the importance of considering the tenocyte toxicity associated with intrathecal and intraneural LA injections, as they might affect tenocytes or reduce the efficacy of associated therapies. Moreover, this study also highlights the protective effects of PRP, which could make LA injections safer.