Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. MATERIALS AND METHODS: A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. RESULTS: A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. CONCLUSIONS: Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. CLINICAL RELEVANCE: The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

PnPP-15, a Synthetic Peptide Derived from a Toxin from Phoneutria nigriventer Spider Venom, Alleviates Diabetic Neuropathic Pain and Acts Synergistically with Pregabalin in Mice.

Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analgesic drugs is necessary, given the limitations that current drugs present. Combining drugs to treat neuropathic pain has been attracting interest to improve their efficacy compared to single-drug monotherapies while also reducing dose sizes to minimize side effects. The aim of our study was to verify the antinociceptive effect of a synthetic peptide, PnPP-15, alone and combined with pregabalin, in male Swiss diabetic mice using the von Frey method. PnPP-15 is a synthetic peptide derived from PnPP19, a peptide representing a discontinuous epitope of the primary structure of the toxin PnTx2-6 from the venom of the spider Phoneutria nigriventer. The antinociceptive activity of both compounds was dose-dependent and showed synergism, which was verified by isobolographic analysis. Treatment with PnPP-15 did not cause spontaneous or forced motor changes and did not cause any damage or signs of toxicity in the analyzed organs (pancreas, lung, heart, kidney, brain, or liver). In conclusion, PnPP-15 is a great candidate for an analgesic drug against neuropathic pain caused by diabetes and exerts a synergistic effect when combined with pregabalin, allowing for even more efficient treatment.

Pregabalin and gabapentin for chronic low back pain without radiculopathy: a systematic review.

BACKGROUND: Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or neuropathy. Therefore, determining their efficacy and safety is of enormous value. OBJECTIVE: To examine the efficacy and safety of using gabapentin and pregabalin for CLBP without radiculopathy or neuropathy. METHODS: We performed a search on the CENTRAL, MEDLINE, EMBASE, LILACS, and Web of Science data bases for clinical trials, cohorts, and case-control studies that evaluated patients with CLBP without radiculopathy or neuropathy for at least eight weeks. The data were extracted and inserted into a previously-prepared Microsoft Excel spreadsheet; the outcomes were evaluated using the Cochrane RoB 2 tool, and the quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Of the 2,230 articles identified, only 5 were included, totaling 242 participants. In them, pregabalin was slightly less efficacious than amitriptyline, the combination of tramadol/acetaminophen, and celecoxib, and pregabalin added to celecoxib showed no benefit when compared to celecoxib alone (very low evidence for all). On the other hand, although one study with gabapentin did not support its use in a general sample of patients with low back pain, another found a reduction in the pain scale and improved mobility (moderate evidence). No serious adverse events were observed in any of the studies. CONCLUSION: Quality information to support the use of pregabalin or gabapentin in the treatment of CLBP without radiculopathy or neuropathy is lacking, although results may suggest gabapentin as a viable option. More data is needed to fill this current gap in knowledge.

ANTECEDENTES: Dor lombar crônica (DLC) é um problema de saúde global, e a gabapentina e a pregabalina são frequentemente utilizadas no tratamento de pacientes sem radiculopatia ou neuropatia associada. Por isso, determinar sua eficácia e segurança é de enorme valor. OBJETIVO: Examinar a eficácia e segurança do uso de gabapentina e pregabalina no tratamento da DLC sem radiculopatia ou neuropatia. MéTODOS: Realizamos uma pesquisa nas bases de dados CENTRAL, MEDLINE, EMBASE, LILACS e Web of Science por ensaios clínicos, coortes e estudos de caso e controle que avaliassem pacientes com DLC sem radiculopatia ou neuropatia por pelo menos oito semanas. Os dados foram extraídos e inseridos em uma planilha previamente elaborada no programa Microsoft Excel; os desfechos foram avaliados com a ferramenta RoB 2 tool da Cochrane, e a qualidade das evidências, pelo sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: Dos 2.230 artigos identificados, apenas 5 foram incluídos, com um total de 242 participantes. Neles, a pregabalina foi ligeiramente menos eficaz do que a amitriptilina, a combinação de tramadol/acetaminofeno, e o celecoxibe, assim como a pregabalina adicionada ao celecoxibe não mostrou benefício em comparação ao uso isolado de celecoxibe (evidência muito baixa para todos). Quanto à gabapentina, embora um estudo não respalde seu uso para uma amostra geral de pacientes com lombalgia, outro encontrou redução na escala de dor e melhora da mobilidade (evidência moderada). Nenhum evento adverso grave foi observado nos estudos. CONCLUSãO: Há carência de informações de qualidade que sustentem o uso de pregabalina ou gabapentina no tratamento da DLC sem radiculopatia ou neuropatia, embora resultados possam sugerir que a gabapentina é uma opção viável. Mais dados são necessários para preencher essa atual lacuna no conhecimento.

Oral pregabalin is effective as preemptive analgesia in abdominal hysterectomy-A randomized controlled trial.

Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever-increasing relevance. Opioid-sparing strategies, such as multimodal analgesia, are trends in this scenario. Pregabalin is a well-established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double-blind, placebo-controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty-five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy.

Does pregabalin act in pain control after lateral pharyngoplasties and tonsillectomies? A pilot study.

OBJECTIVE: Some studies have pointed to gabapentinoids as promising medications in postoperative pain control. The objective of the present study was to evaluate the efficacy of pregabalin in reducing postoperative pain in tonsillectomy and lateral pharyngoplasties. STUDY DESIGN: Double-blind randomized controlled trial. SETTING: Tertiary care center. METHODS: A double-blind randomized controlled trial was conducted with patients undergoing tonsillectomies and lateral pharyngoplasties between Aug 29, 2017, and Oct 31, 2020. Data of interest such as opioid consumption, pain scores, and adverse outcomes such as dizziness, nausea, headache, and sedation within 7 days following surgeries were analyzed. RESULTS: No statistically significant difference was observed in pain scores and opioid consumption between the groups studied in the pilot project. The use of pregabalin was associated with lower incidence of dizziness compared to controls. CONCLUSION: Gabapentinoids, especially pregabalin, are drugs whose potential for controlling pain after pharyngeal surgery, such as tonsillectomy and sleep apnea surgery, still needs to be more fully evaluated. After the conclusion of the present study, we hope to answer this question about the role of pregabalin in oropharyngeal surgeries.

Medidas para optimizar cuidados post rinoplastia. Revisión sistemática de la literatura / Measures to optimize rhinoplasty post operative care, systematic review of the literature

Introducción: El cuidado postoperatorio de la rinoplastia ha evolucionado, paralelamente, al desarrollo de la técnica quirúrgica. Existen varias recomendaciones, sin embargo, hay una gran variabilidad interprofesional de las indicaciones post quirúrgicas. Objetivo: Realizar una revisión sistemática de la literatura científica sobre los cuidados post operatorios de la rinoplastia. Material y Método: Para la realización de este estudio se llevaron a cabo búsquedas en PubMed y en Cochrane Database of Systematic Reviews con los perfiles: ([rhinoplasty] AND [post operative care]) y ([rhinoplasty] AND [post surgical care]). Se seleccionaron los artículos publicados en los últimos 10 años, desde 2013 hasta 2023, ambos inclusive. Resultados: Los documentos analizados recogen la evidencia de los diferentes métodos de cuidados post quirúrgicos en rinoplastia. Estos confirman la utilización de corticoides en el período postoperatorio, así como el reposo en 90° y exponen la variabilidad interprofesional que existe en el protocolo postquirúrgico de esta cirugía. Conclusión: El uso de corticoides y el reposo en 90° disminuyen las complicaciones postquirúrgicas de la rinoplastia. Debe existir una clara información sobre lo que el paciente debe esperar post cirugía. El uso de opioides debe ser restringido y la analgesia debe ser multimodal. Es preciso realizar estudios futuros con mayor nivel de evidencia y tener protocolos uniformes para la práctica clínica.

Introduction: The postoperative care of rhinoplasty has evolved along with the development of the surgical technique. There are several recommendations, however there is enormous interprofessional variability of post-surgical indications. Aim: To carry out a systematic review of the scientific literature on rhinoplasty postoperative care. Material and Method: To carry out this study, searches were carried out in PubMed and in the Cochrane Database of Systematic Reviews with the profiles: ([rhinoplasty] AND [post operative care]) and ([rhinoplasty] AND [post surgical care]). Articles published in the last 10 years were selected, from 2013 to 2023, both inclusive. Results: The documents analyzed collect the evidence of the different methods of post-surgical care in rhinoplasty, they confirm the use of corticosteroids in the postoperative period as well as rest at 90° and expose the interprofessional variability that exists in the post-surgical protocol of this surgery. Conclusion: The use of corticosteroids and rest at 90° reduce the post-surgical complications of rhinoplasty. There must be clear information about what the patient should expect post surgery. The use of opioids must be restricted and analgesia must be multimodal. It is necessary to carry out future studies with a higher level of evidence and have uniform protocols for clinical practice.

Pregabalin synchronizes the regeneration of nerve and muscle fibers optimizing the gait recovery of MDX dystrophic mice.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder induced by mutations in the dystrophin gene, leading to a degeneration of muscle fibers, triggering retrograde immunomodulatory, and degenerative events in the central nervous system. Thus, neuroprotective drugs such as pregabalin (PGB) can improve motor function by modulating plasticity, together with anti-inflammatory effects. The present work aimed to study the effects of PGB on axonal regeneration after axotomy in dystrophic and non-dystrophic mice. For that, MDX and C57BL/10 mouse strains were subjected to peripheral nerve damage and were treated with PGB (30 mg/kg/day, i.p.) for 28 consecutive days. The treatment was carried out in mice as soon as they completed 5 weeks of life, 1 week before the lesion, corresponding to the peak period of muscle degeneration in the MDX strain. Six-week-old mice were submitted to unilateral sciatic nerve crush and were sacrificed in the 9th week of age. The ipsi and contralateral sciatic nerves were processed for immunohistochemistry and qRT-PCR, evaluating the expression of proteins and gene transcripts related to neuronal and Schwann cell activity. Cranial tibial muscles were dissected for evaluation of neuromuscular junctions using α-bungarotoxin, and the myelinated axons of the sciatic nerve were analyzed by morphometry. The recovery of motor function was monitored throughout the treatment through tests of forced locomotion (rotarod) and spontaneous walking track test (Catwalk system). The results show that treatment with PGB reduced the retrograde cyclic effects of muscle degeneration/regeneration on the nervous system. This fact was confirmed after peripheral nerve injury, showing better adaptation and response of neurons and glia for rapid axonal regeneration, with efficient muscle targeting and regain of function. No side effects of PGB treatment were observed, and the expression of pro-regenerative proteins in neurons and Schwann cells was upregulated. Morphometry of the axons was in line with the preservation of motor endplates, resulting in enhanced performance of dystrophic animals. Overall, the present data indicate that pregabalin is protective and enhances regeneration of the SNP during the development of DMD, improving motor function, which can, in turn, be translated to the clinic.

The Effect of Neuromodulatory Drugs on the Intensity of Chronic Pelvic Pain in Women: A Systematic Review.

OBJECTIVE: To evaluate the effect of neuromodulatory drugs on the intensity of chronic pelvic pain (CPP) in women. DATA SOURCES: Searches were carried out in the PubMed, Cochrane Central, Embase, Lilacs, OpenGrey, and Clinical Trials databases. SELECTION OF STUDIES: The searches were carried out by two of the authors, not delimiting publication date or original language. The following descriptors were used: chronic pelvic pain in women OR endometriosis, associated with MESH/ENTREE/DeCS: gabapentinoids, gabapentin, amitriptyline, antidepressant, pregabalin, anticonvulsant, sertraline, duloxetine, nortriptyline, citalopram, imipramine, venlafaxine, neuromodulation drugs, acyclic pelvic pain, serotonin, noradrenaline reuptake inhibitors, and tricyclic antidepressants, with the Boolean operator OR. Case reports and systematic reviews were excluded. DATA COLLECTION: The following data were extracted: author, year of publication, setting, type of study, sample size, intervention details, follow-up time, and results. DATA SYNTHESIS: A total of 218 articles were found, with 79 being excluded because they were repeated, leaving 139 articles for analysis: 90 were excluded in the analysis of the titles, 37 after reading the abstract, and 4 after reading the articles in full, and 1 could not be found, therefore, leaving 7 articles that were included in the review. CONCLUSION: Most of the studies analyzed have shown pain improvement with the help of neuromodulators for chronic pain. However, no improvement was found in the study with the highest statistical power. There is still not enough evidence that neuromodulatory drugs reduce the intensity of pain in women with CPP.

OBJETIVO: Avaliar o efeito de drogas neuromoduladoras na intensidade da dor pélvica crônica em mulheres. FONTES DE DADOS: As buscas foram realizadas nas bases de dados PubMed, Cochrane Central, Embase, Lilacs, OpenGrey e Clinical Trials. SELEçãO DOS ESTUDOS:: As buscas foram realizadas por dois dos autores, não delimitando data de publicação ou idioma de publicação. Foram usados os seguintes descritores: chronic pelvic pain in women OR endometriosis, associated with MESH/ENTREE/DeCS: gabapentinoids, gabapentin, amitriptyline, antidepressant, pregabalin, anticonvulsant, sertraline, duloxetine , nortriptyline, citalopram, imipramine, venlafaxine, neuromodulation drugs, acyclic pelvic pain, serotonin, noradrenaline reuptake inhibitors e tricyclic antidepressants, com o operador booleano OR. Relatos de caso e revisões sistemáticas foram excluídos. COLETA DE DADOS: Foram extraídos os seguintes dados: autor, ano de publicação, local de origem, tipo de estudo, tamanho da amostra, detalhes da intervenção, tempo de seguimento e resultados. SíNTESE DOS DADOS:: Foram encontrados 218 artigos, sendo 79 deles excluídos por serem repetidos, restando 139 artigos para análise, dos quais 90 foram excluídos na análise dos títulos, 37 após a leitura do resumo e 4 após a leitura dos artigos na íntegra, e 1 não foi encontrado, restando, então, 7 artigos que foram incluídos na revisão. CONCLUSãO:: A maioria dos estudos analisados mostrou melhora da dor crônica com auxílio de neuromoduladores. No entanto, nenhuma melhora foi encontrada no artigo com maior poder estatístico. Ainda não há evidências suficientes de que drogas neuromoduladoras reduzam a intensidade da dor pélvica crônica em mulheres.

Comparison of the effects of duloxetine and pregabalin on pain and associated factors in patients with knee osteoarthritis.

OBJECTIVES: This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on quality of life, depression, anxiety, and sleep disturbance. METHODS: A total of 66 patients with knee osteoarthritis were randomized to use duloxetine or pregabalin. Patients were evaluated by Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36, Beck Depression Inventory, Beck Anxiety Inventory, and Pittsburg Sleep Quality Index before the treatment and after 4 and 12 weeks of treatment. RESULTS: Improvements occurred in Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36 (with an exception of the mental health subgroup scores in duloxetine-treated group), Beck Depression Inventory, and Beck Anxiety Inventory scores in both groups from 4 weeks after baseline. Pittsburg Sleep Quality Index total scores and SF-36 mental health subgroup scores started to improve on the 4th and 12th weeks in pregabalin- and duloxetine-treated groups, respectively. CONCLUSION: Osteoarthritis pain, a complex outcome with nociceptive and neuropathic components, leads to central sensitization in a chronic phase. Using centrally acting drugs in the control of pain and associated symptoms would increase the probability of treatment success.

Comparative efficacy of amitriptyline, duloxetine and pregabalin for treating fibromyalgia in adults: an overview with network meta-analysis.

Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18 years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3 months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450 mg was superior to DLX 30 mg and PGB 150 mg, while DLX 20 mg and 30 mg were not superior to placebo. For the outcome R50%, AMT 25 mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450 mg was the best performance option for R30% and AMT 25 mg for R50%. PGB 150 mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison studies, indirect comparison meta-analyses are an important resource for assisting in clinical decision-making. Our data only provide an indicator of the effectiveness of the three drugs evaluated, but as with other health conditions, tolerability and safety are important for the decision-making process and clinical management. In this regard, we encourage caution in interpreting our data.

A single injection of pregabalin induces short- and long-term beneficial effects on fear memory and anxiety-like behavior in rats with experimental type-1 diabetes mellitus.

Anxiety Disorders and Posttraumatic Stress Disorders (PTSD) associated with type-1 diabetes mellitus (T1DM) are increasingly common comorbidities and the treatment is quite challenging. In that sense, evidence indicates that the anticonvulsant pregabalin is highly effective in treating severe cases of anxiety, as well as PTSD and diabetic neuropathic pain which is also very prevalent in T1DM. Herein, the short- and long-term effects of a single injection of pregabalin on the acquisition of a fear extinction memory and parameters of anxiety in induced-T1DM animals were investigated. For that, we used the contextual fear conditioning (CFC) and elevated plus maze paradigms, respectively. A putative antioxidant activity was also evaluated. Our findings demonstrated that induced-T1DM animals presented greater expression of fear memory, difficulty in extinguishing this fear memory, associated with a more pronounced anxiety-like response. Pregabalin was able to induce a short and long-lasting effect by facilitating the acquisition of the fear extinction memory and inducing a later anxiolytic-like effect. Also, the increased lipid peroxidation levels in the hippocampus and prefrontal cortex of induced-T1DM rats were reduced after pregabalin injection, while the decreased levels of reduced glutathione were increased in the hippocampus. Despite the need for more studies to understand the mechanism of action of pregabalin under these conditions, our data demonstrate for the first time that a single injection of pregabalin in a specific time window was able to improve behavioral parameters in addition to inducing neuroprotective effect. Thus, pregabalin has potential worth exploring for the treatment of PTSD and/or Anxiety associated with T1DM.

Dry needling increases antioxidant activity and grip force in a rat model of muscle pain.

BACKGROUND: Muscle pain syndromes (MPS) are one of the main causes of functional, structural and metabolic problems, being associated with tissue oxidative damage. Although dry needling is widely used in the treatment of MPS, there is little scientific evidence of its efficacy and underlying mechanisms of action. OBJECTIVES: To investigate the effects of different dry needling techniques on thermal and mechanical hyperalgesia, locomotor and functional activity, and oxidative stress markers in a rat model of muscle pain. METHODS: A total of 48 male Wistar rats underwent injection of the gastrocnemius muscle with control neutral saline (pH 7) and remained untreated (Saline group), or acidic saline (pH 4) and remained untreated (ASA group) or received pregabalin (PG group), deep needling (DN group), superficial needling (SN group) or twitch needling (TN group) with n = 8 rats per group. Mechanical (von Frey test) and thermal hyperalgesia (acetone test), muscle edema (assessed with a caliper), strength and muscle function (grip force evaluation), surface thermography and locomotor and exploratory activities (open field test) were evaluated. The animals were then euthanized, and the gastrocnemius muscle was excised for assessment of oxidative analyses of lipid peroxidation with thiobarbituric acid reactive species (TBA-RS) and total glutathione (GSH) levels. RESULTS: All treatments significantly improved muscle strength and function when compared to the AS group (p < 0.05). Pregabalin reduced locomotor and exploratory activities, while the TN intervention increased the antioxidant response (p < 0.05). CONCLUSION: Dry needling improved strength, functionality and locomotor activity in a rat model of muscle pain. Twitch needling induced an antioxidant effect.

Precise and Sensitive Ambient Temperature Based Analytical Colorimetric Method for Pregabalin

Abstract Pregabalin, a GABA analogue is used to treat epilepsy and neuropathic pain. The drug poses problems in analytical quantification when estimated at a shorter UV wavelength. The expensive and non-repetitive reported analytical methods necessitate the utility and development of an accurate, precise, repetitive, simple and highly sensitive colorimetric method for pregabalin in solution as well as sustained release mini matrices. Pregabalin (having primary amino group) was derivatized at alkaline pH of mixture with optimized ninhydrin solution at ambient temperature (25oC). The ninhydrin-pregabalin derivatized complex (Ruhemann's Purple) was analyzed for drug concentration at absorption maximum (λmax) of 570nm. The linearity was observed in the concentration range of 5-150 µg/mL with coefficient of correlation, 0.998. The developed analytical method was validated according to ICH guidelines and proved to be highly sensitive (LOD 0.917µg/mL, LOQ 3.055µg/mL), with good inter-day as well as intra-day accuracy and precision as 4.65% and 3.75%, respectively. The proposed method was proved to be a simple, sensitive, precise and accurate for the estimation of the minute concentrations of pregabalin in pure form and the developed formulations. Results verified that the proposed method could determine pregabalin at the ambient temperature without requiring high temperatures used in the existing methods. It was concluded that developed method was easier and more suitable for analysis of pregabalin in quality control of commercial preparations

Investigation of the Combination of Pregabalin with Duloxetine or Amitriptyline on the Pharmacokinetics and Antiallodynic Effect During Neuropathic Pain in Rats.

BACKGROUND: Amitriptyline, duloxetine, and pregabalin are among the most pharmacotherapeutic, effective treatments for neuropathic pain control. However, the evaluation of synergism by combining these treatments is still poorly investigated. OBJECTIVES: To evaluate the pharmacokinetics of the combination of pregabalin plus duloxetine and pregabalin plus amitriptyline, as well as the effect of these on neuropathic pain on rodent model. STUDY DESIGN: The experimental study. SETTING: The research took place in the research laboratories at the Federal University of Alfenas after ethics committee approval. METHODS: This study used male Wistar rats weighing between 220 and 250 g. The animals were randomly divided into the following groups: monotherapy (pregabalin, amitriptyline, duloxetine), combined therapy (pregabalin + amitriptyline, pregabalin + duloxetine), and vehicle (ultrapure water). Pharmacokinetic analysis of pregabalin or combination (pregabalin + amitriptyline or pregabalin + duloxetine) in the plasma were performed by ultraperformance liquid chromatography tandem mass spectrometry. Neuropathic pain was induced by sciatic nerve constriction (chronic constriction injury [CCI]) model, and nociceptive threshold was measured by von Frey filaments test. In addition, to evaluate the influence of the treatments on the motor coordination, the rotarod test was used. RESULTS: The pharmacokinetic disposition of pregabalin was changed in the association with amitriptyline, presenting a clearance reduction and consequently an increase in bioavailability. Furthermore, after the 14th day of CCI, pregabalin was administered orally and induced antiallodynic effect after 1, 2:15, 4, and 8 hours of its administration and showed the greatest antiallodynic effect after 4 hours of its administration. Moreover, this effect was prolonged (up to 8 hours) by combination with amitriptyline. Additionally, pregabalin and pregabalin + duloxetine showed a hypoalgesic effect in sham rats. In addition, the rotarod test results showed that drugs did not influence the motor coordination of the rats. LIMITATIONS: Potential competition mechanisms during the excretion of pregabalin, when pregabalin was combined with amitriptyline, were not investigated in this study. CONCLUSIONS: The data demonstrated that combined therapy of pregabalin plus amitriptyline improved the bioavailability of pregabalin and potentiated the efficacy of the antiallodynic effect of pregabalin alone, proving to be advantageous for the treatment of sciatic neuropathic pain.

Pregabalina para o tratamento de dor neuropática e fibromialgia / Pregabalin for pain management neuropathic and fibromyalgia

INTRODUÇÃO: A dor neuropática é causada por lesões ou doenças que afetam o sistema somatossensorial, caracterizada por dor espontânea ou anormal evocada por estímulo. Por outro lado, a fibromialgia é uma condição crônica caracterizada por dor musculoesquelética generalizada, fadiga, distúrbios do sono, comprometimento cognitivo e ansiedade, sem uma etiologia conhecida. No Brasil, no âmbito do Sistema Único de Saúde (SUS), o tratamento da dor crônica é direcionado, atualmente, pelo Protocolo Clínico e Diretrizes Terapêuticas da Dor Crônica. Dada a complexidade do tratamento da dor crônica neuropática e a ausência de tratamento medicamentoso para tratar a fibromialgia, o presente relatório foi elaborado com o objetivo de compreender a viabilidade do uso de pregabalina no manejo dessas condições clínicas, visando sua possível incorporação no SUS. TECNOLOGIA: Pregabalina (ALOND®, ÁPICE®, DORENE®, DORENE TABS®, GABALGIN®, GLYA®, INSIT®, KONDUZ®, LIMIAR®, LYRICA®, LYSUGI®, MOBALE®, NEUGABA®, PREBICTAL®, PREFISS®, PREGALPHA®, PRENEURIN®, PROLEPTO®, VOLVER®). PERGUNTA: Pregabalina é eficaz, segura e custo-efetiva para o tratamento de pacientes adultos com dor neuropática e fibromialgia, co

Pregabalina para o tratamento de dor neuropática e fibromialgia / Pregabalin for Pain Treatment neuropathic and fibromyalgia

INTRODUÇÃO: A dor neuropática é causada por lesões ou doenças que afetam o sistema somatossensorial, caracterizada por dor espontânea ou anormal evocada por estímulo. Por outro lado, a fibromialgia é uma condição crônica caracterizada por dor musculoesquelética generalizada, fadiga, distúrbios do sono, comprometimento cognitivo e ansiedade, sem uma etiologia conhecida. No Brasil, no âmbito do Sistema Único de Saúde (SUS), o tratamento da dor crônica é direcionado, atualmente, pelo Protocolo Clínico e Diretrizes Terapêuticas da Dor Crônica. Dada a complexidade do tratamento da dor crônica neuropática e a ausência de tratamento medicamentoso para tratar a fibromialgia, o presente relatório foi elaborado com o objetivo de compreender a viabilidade do uso de pregabalina no manejo dessas condições clínicas, visando sua possível incorporação no SUS. TECNOLOGIA: Pregabalina (ALOND®, ÁPICE®, DORENE®, DORENE TABS®, GABALGIN®, GLYA®, INSIT®, KONDUZ®, LIMIAR®, LYRICA®, LYSUGI®, MOBALE®, NEUGABA®, PREBICTAL®, PREFISS®, PREGALPHA®, PRENEURIN®, PROLEPTO®, VOLVER®). PERGUNTA: Pregabalina é eficaz, segura e custo-efetiva para o tratamento de pacientes adultos com dor neuropática e fibromialgia, comparada a gabapenti

The effects of pregabalin, solifenacin and their combination therapy on ureteral double-J stent-related symptoms: A randomized controlled clinical trial

ABSTRACT Background: Many medical therapies have been tested to deal with urinary stent-related symptoms (USRS). Several preventive and pharmaceutical methods have been already used for better compatibility of stents. However, the existing evidence for pharmacological treatment is still controversial. This study aims to evaluate the effects of pregabalin, solifenacin, and combination therapy on ureteral double-J stent-related symptoms following ureteroscopy and transureteral lithotripsy (TUL). Materials and methods: In a randomized controlled clinical trial, from November 2017 to March 2019, 256 patients who underwent ureteroscopy were enrolled. Patients were randomly divided into four groups including: group A received pregabalin 75mg BID (twice daily), group B received solifenacin 5mg orally once daily, group C received combination of pregabalin and solifenacin and the group D (control) given no drugs. Results: One hundred and fifty-one (58.9%) males and 101 (41.1%) females were enrolled in this study with a mean age of 43.47±7 (p=0.32, p=0.67). USSQ domains score such as urinary symptoms, pain, general condition, work performance, sexual matters and additional problems were significantly differenced during second and fourth week of follow-up among study groups (p <0.0001). In Tukey's multiple comparison test, urinary symptoms (p=0.735), pain (p=0.954) and sexual matters (p=0.080) in second week and work performance in forth week in group B was not significantly better than group D. Only group C in all indexes of USSQ showed significantly beneficial effects over group D (p <0.0001). Conclusion: Combination therapy of pregabalin and solifenacin has a significant effect on stent-related symptoms and is preferred over monotherapy of the respected medications.

Pregabalin-induced neuroprotection and gait improvement in dystrophic MDX mice.

Duchenne muscular dystrophy (DMD) is a genetic disease linked to the X chromosome induced by mutations in the dystrophin gene. Neuroprotective drugs, such as pregabalin (PGB), can improve motor function through the modulation of excitatory synapses, together with anti-apoptotic and anti-inflammatory effects. The present work studied the effects of PGB in the preservation of dystrophic peripheral nerves, allowing motor improvements in MDX mice. Five weeks old MDX and C57BL/10 mice were treated with PGB (30 mg/kg/day, i.p.) or vehicle, for 28 consecutive days. The mice were sacrificed on the 9th week, the sciatic nerves were dissected out and processed for immunohistochemistry and qRT-PCR, for evaluating the expression of proteins and gene transcripts related to neuronal activity and Schwann cell function. The lumbar spinal cords were also processed for qRT-PCR to evaluate the expression of neurotrophic factors and pro- and anti-inflammatory cytokines. Cranial tibial muscles were dissected out for endplate evaluation with α-bungarotoxin. The recovery of motor function was monitored throughout the treatment, using a spontaneous walking track test (Catwalk system) and a forced locomotion test (Rotarod). The results showed that treatment with PGB reduced the retrograde effects of muscle degeneration/regeneration on the nervous system from the 5th to the 9th week in MDX mice. Thus, PGB induced protein expression in neurons and Schwann cells, protecting myelinated fibers. In turn, better axonal morphology and close-to-normal motor endplates were observed. Indeed, such effects resulted in improved motor coordination of dystrophic animals. We believe that treatment with PGB improved the balance between excitatory and inhibitory inputs to spinal motoneurons, increasing motor control. In addition, PGB enhanced peripheral nerve homeostasis, by positively affecting Schwann cells. In general, the present results indicate that pregabalin is effective in protecting the PNS during the development of DMD, improving motor coordination, indicating possible translation to the clinic.