PREGABALIN AS A PREOPERATIVE ADJUVANT IN PATIENTS WITH CARPAL TUNNEL SYNDROME.

Objective: To evaluate the pregabalin adjuvant effect in patients with carpal tunnel syndrome (CTS) surgically treated, analyzing postoperative pain and the incidence of complex regional pain syndrome (CRPS). Methods: Outpatient surgical candidates with CTS were selected and followed for 12 months, divided into three groups. The Control Group received a placebo, the Pregabalin 75mg Group received a daily dose, and the Pregabalin 150mg Group received a daily dose of the medication. Patient progress was evaluated using the visual analog scale (VAS) for pain and the DN4 neuropathic pain score before surgery, one month and three months after. Results: The administration of pregabalin to surgical patients with CTS did not demonstrate significant differences in immediate postoperative pain relief. Additionally, there were no statistically significant variations in the incidence of complications, such as CRPS, among the groups. Conclusion: This study did not show a significant impact of pregabalin on postoperative pain relief or the reduction of CRPS incidence in patients undergoing surgery for CTS. These results suggest that pregabalin might not be an effective adjuvant in these surgical situations. Level of evidence II (Oxford), Prospective Comparative Study.

Objetivo: Avaliar o efeito adjuvante da pregabalina em pacientes com síndrome do túnel do carpo (STC) tratados cirurgicamente, analisando a dor pós-operatória e a incidência da síndrome da dor complexa regional (SDCR). Métodos: Foram selecionados pacientes com acompanhamento ambulatorial e indicação de tratamento cirúrgico para STC, sendo acompanhados ao longo de 12 meses e divididos em três grupos. O Grupo Controle recebeu placebo, o Grupo Pregabalina 75 mg tomou uma dose diária da medicação citada e o Grupo Pregabalina 150 mg também recebeu uma dose diária da medicação, em maior quantidade. A evolução dos pacientes foi avaliada mediante aplicação da escala visual analógica de dor (EVA) e escore de dor neuropática DN4 antes da cirurgia, um mês e três meses após essa. Resultados: A administração de pregabalina em pacientes cirúrgicos com STC não demonstrou diferenças significativas no alívio da dor pós-operatória imediata. Além disso, não houve variações estatisticamente significativas na incidência de complicações, como a SDCR, entre os grupos. Conclusão: Este estudo não evidenciou um impacto significativo da pregabalina no alívio da dor pós-operatória ou na redução da incidência da SDCR em pacientes submetidos a cirurgia para STC. Estes resultados sugerem que a pregabalina pode não ser um adjuvante eficaz nessas situações cirúrgicas. Nível II de Evidência (Oxford), Estudo prospectivo comparativo.

Characterization and Evaluation of the Cytotoxicity of Pregabalin Gels for Oral Application.

The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral cavity. Solutions with three different concentrations of PG were prepared and added to a 1.0% carbopol gel base. Thermal analyses (TG and DSC) and FTIR were performed on the gel and pure pregabalin. Stability (preliminary and accelerated) and rheology studies were also conducted on the gels. Cytotoxicity was evaluated in human gingival fibroblasts in the following groups: WG (1.0% carbopol gel base), PG2G (2.0% pregabalin gel), PG5G (5.0% pregabalin gel), and PG10G (10% pregabalin gel). A transparent and homogeneous gel with a pH of 6 was obtained. The formulations showed stability, and the different drug concentrations did not influence the product's characteristics. None of the tested groups showed cytotoxicity for the analyzed cells. The pregabalin gels exhibited favorable and non-toxic characteristics for human gingival fibroblasts in vitro. Therefore, this product may be a promising therapeutic alternative for topical application in the oral mucosa.

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.

Pregabalin as a preoperative adjuvant in patients with carpal tunnel syndrome / Ação da pregabalina como adjuvante no pré operatório em pacientes com síndrome do túnel do carpo

ABSTRACT Objective: To evaluate the pregabalin adjuvant effect in patients with carpal tunnel syndrome (CTS) surgically treated, analyzing postoperative pain and the incidence of complex regional pain syndrome (CRPS). Methods: Outpatient surgical candidates with CTS were selected and followed for 12 months, divided into three groups. The Control Group received a placebo, the Pregabalin 75mg Group received a daily dose, and the Pregabalin 150mg Group received a daily dose of the medication. Patient progress was evaluated using the visual analog scale (VAS) for pain and the DN4 neuropathic pain score before surgery, one month and three months after. Results: The administration of pregabalin to surgical patients with CTS did not demonstrate significant differences in immediate postoperative pain relief. Additionally, there were no statistically significant variations in the incidence of complications, such as CRPS, among the groups. Conclusion: This study did not show a significant impact of pregabalin on postoperative pain relief or the reduction of CRPS incidence in patients undergoing surgery for CTS. These results suggest that pregabalin might not be an effective adjuvant in these surgical situations. Level of evidence II (Oxford), Prospective Comparative Study.

RESUMO Objetivo: Avaliar o efeito adjuvante da pregabalina em pacientes com síndrome do túnel do carpo (STC) tratados cirurgicamente, analisando a dor pós-operatória e a incidência da síndrome da dor complexa regional (SDCR). Métodos: Foram selecionados pacientes com acompanhamento ambulatorial e indicação de tratamento cirúrgico para STC, sendo acompanhados ao longo de 12 meses e divididos em três grupos. O Grupo Controle recebeu placebo, o Grupo Pregabalina 75 mg tomou uma dose diária da medicação citada e o Grupo Pregabalina 150 mg também recebeu uma dose diária da medicação, em maior quantidade. A evolução dos pacientes foi avaliada mediante aplicação da escala visual analógica de dor (EVA) e escore de dor neuropática DN4 antes da cirurgia, um mês e três meses após essa. Resultados: A administração de pregabalina em pacientes cirúrgicos com STC não demonstrou diferenças significativas no alívio da dor pós-operatória imediata. Além disso, não houve variações estatisticamente significativas na incidência de complicações, como a SDCR, entre os grupos. Conclusão: Este estudo não evidenciou um impacto significativo da pregabalina no alívio da dor pós-operatória ou na redução da incidência da SDCR em pacientes submetidos a cirurgia para STC. Estes resultados sugerem que a pregabalina pode não ser um adjuvante eficaz nessas situações cirúrgicas. Nível II de Evidência (Oxford), Estudo prospectivo comparativo.

Estudo de fase II de pregabalina para prevenção de náuseas e vômitos induzidos por quimioterapia / Phase II study of pregabalin for the prevention of chemotherapy induced nausea and vomiting

Para avaliar o papel da pregabalina na proteção das náuseas e vômitos induzidos pela quimioterapia, foi realizado um ensaio clínico de fase II, aleatorizado, duplamente cego, controlado por placebo, para investigar se a pregabalina poderia melhorar o controle completo das náuseas e vômitos (desfecho primário). Inscrevemos 82 pacientes virgens de quimioterapia, programados para receber quimioterapia moderadamente e altamente emetogênica. Todos os doentes receberam ondansetron 8mg por via intravenosa, dexametasona 10mg antes da quimioterapia no primeiro dia e, dexametasona 4 mg por via oral, b.d., nos dias dois e três. Os doentes foram distribuídos aleatoriamente para tomar pregabalina 75 mg ou placebo, bd, desde a noite anterior à quimioterapia até ao quinto dia. A resposta completa global não foi estatisticamente significativa entre os grupos (53,7 versus 48,8%, respetivamente, no grupo da pregabalina e no grupo de controlo (P=0,65)). Também não houve diferença estatística significativa durante a fase aguda (primeiras 24 horas) e a fase tardia (24-120h): 80,5% versus 82,9% (P=0,77), 53,7 versus 51,2% (P=0,82), respectivamente. Neste estudo não foi identificada ação da pregabalina na prevenção de náuseas e vômitos induzidos por quimioterapia. Número de registo no Clinicaltrial.gov: NCT04181346.

To evaluate the role of pregabalin in the protection of chemotherapy-induced nausea and vomiting, we performed a phase II randomized, double-blind, placebo-controlled trial to investigate whether pregabalin could improve the complete control of nausea and vomiting (primary end point). We enrolled 82 chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy. All patients received IV ondansetron 8mg, dexamethasone 10mg before chemotherapy on day one and oral dexamethasone 4mg, b.d., on days two and three. Patients were randomly assigned to take pregabalin 75mg or placebo, bd, from the night before chemotherapy to day five. The overall complete response was not statistically significant between the groups (53.7 versus 48.8%, respectively, in the pregabalin group and the control group (P=0.65)). There was also no significant difference during the acute phase (first 24 hours) and delayed phase (24-120h): 80.5% versus 82.9% (P=0.77), 53.7 versus 51.2% (P=0.82), respectively. There is no role for pregabalin preventing chemotherapy-induced nausea and vomiting. Clinicaltrial.gov registration number: NCT04181346.

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.

Preoperative pregabalin prevents succinylcholine-induced fasciculation and myalgia: A meta-analysis of randomized trials.

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction; however, its use is associated with fasciculation and myalgia. We performed a systematic review and meta-analysis of randomized controlled clinical trials comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included with a total of 481 patients - 241 in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR = 0.69, 95% CI 0.56-0.84, P < .001), which remained statistically significant for pregabalin (RR = 0.71, 95% CI 0.54-0.93, P = .013) and gabapentin (RR = 0.61, 95% CI 0.45-0.82, P = .001) separately. There was no difference in fasciculations between the groups (RR = 0.92, 95% CI 0.82-1.03, P = .148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24 h of surgery.

Pregabalin and gabapentin for chronic low back pain without radiculopathy: a systematic review / Pregabalina e gabapentina para dor lombar crônica sem radiculopatia: uma revisão sistemática

Abstract 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.

Resumo 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.

Treatment patterns in fibromyalgia including the use of opioids.

OBJECTIVE: Opioids (except for tramadol) have not been shown to be effective in patients with fibromyalgia, but they can increase the risk of adverse drug reactions. The aim was to determine the treatment patterns of a group of patients with fibromyalgia and to identify the factors associated with the use of opioids in Colombia. METHODS: This was a cross-sectional study of a group of patients with fibromyalgia from a pain clinic in Colombia. Sociodemographic, clinical and pharmacological variables were identified. Descriptive, bivariate, and multivariate analyses were performed. RESULTS: A total of 559 patients were analysed, 88.6% of whom were women, and the mean age was 53.4 ± 12.6 years. A total of 40.6% received nonpharmacological management, and the majority were treated with acetaminophen (96.1%) and pregabalin (62.8%). A total of 69.6% received opioids, the most common of which was hydrocodone (36.3%). The average morphine equivalent milligrammes was 36.9 ± 91.2 (range: 2.3-750 mg), and 43.8% had intermediate/high doses. Being male (OR: 3.12; 95% CI: 1.40-6.91), having arterial hypertension (OR: 1.67; 95% CI: 1.04-2.69), obesity (OR: 2.23; 95% CI: 1.18-4.24), degenerative disease of vertebral discs (OR: 2.32; 95% CI: 1.10-4.88) and comedication with gabapentinoids (OR: 1.75; 95% CI: 1,15-2.65) were associated with a higher probability of receiving opioids, while patients treated with muscle relaxants had a lower risk of opioid treatment (OR: 0.64; 95% CI: 0.41-0.98). CONCLUSIONS: A significant proportion of patients were treated with opioids, the most common of which was hydrocodone, which goes against the recommendations of clinical practice guidelines.

Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin.

Dysregulated microglia and astrocytes have been associated with progressive neurodegeneration in multiple sclerosis (MS), highlighting the need for strategies that additionally target intrinsic inflammation in the central nervous system (CNS). The objective of the present study was to investigate the glial response in experimental autoimmune encephalomyelitis (EAE)-induced mice treated with a combination of dimethyl fumarate (DMF) and pregabalin (PGB). For that, 28 C57BL/6J mice were randomly assigned to the five experimental groups: naïve, EAE, EAE-DMF, EAE-PGB, and EAE-DMF + PGB. Pharmacological treatments were initiated with the beginning of clinical signs, and all animals were euthanized at 28 dpi for the lumbar spinal cord evaluation. The results demonstrated a stronger attenuation of the clinical presentation by the combined approach. DMF alone promoted the downregulation of Iba-1 (microglia/macrophages marker) in the ventral horn compared with the non-treated EAE animals (P < 0.05). PGB treatment was associated with reduced Iba-1 immunofluorescence in both the dorsal (P < 0.05) and ventral horn (P < 0.05) compared to EAE vehicle-treated counterparts. However, the combined approach reduced the Iba-1 marker in the dorsal (P < 0.05) and ventral (P < 0.01) horns compared to non-treated EAE animals and further reduced Iba-1 in the ventral horn compared to each drug-alone approach (P < 0.05). In addition, the combination of DMF and PGB reduced activated astrocytes (GFAP) in both the dorsal and ventral horns of the spinal cord to a naïve-like level and upregulated Nrf-2 expression. Taken together, the data herein suggest robust attenuation of the glial response in EAE mice treated with DMF and PGB.

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.

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

SUMMARY 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.

Analgesic effect of pregabalin and magnesium sulfate after mastectomy with axillary lymphadenectomy / Efeito analgésico da pregabalina e do sulfato de magnésio no pósoperatório de mastectomia com linfadenectomia axilar

ABSTRACT BACKGROUND AND OBJECTIVES: Mastectomy with lymphadenectomy is a surgery associated with moderate to severe pain in the immediate postoperatory. Several safe adjuvant drugs that provide good analgesia with few adverse effects have been researched. Pregabalin and magnesium sulfate are drugs that promote analgesia with few adverse effects. The objective of the present study was to evaluate the analgesic effect of pregabalin and magnesium sulfate in the postoperatory of mastectomy with axillary lymphadenectomy. METHODS: Double-blinded, randomized study involving 80 patients submitted to mastectomy with axillary lymphadenectomy under general anesthesia. The patients were distributed into 4 groups: Control (CG, did not receive the proposed adjuvant drug); Magnesium+Placebo (MG, received magnesium sulfate during anesthesia); Pregabalin+Magnesium (P+MG, received magnesium added to pregabalin 150 mg before and 12 h after surgery); and Pregabalin+Placebo (PG, received pregabalin). All patients completed the Self-Report Questionnaire 20 (SRQ-20) to screen for possible mental disorders and had their physical status monitored at 1 h, 12 h, and 24 h after surgery, through anamnesis, pain questionnaire, opioid consumption, and presence of complications and/or adverse events such as nausea, vomiting, and sleepiness. Randomization was performed using sealed opaque envelopes without the knowledge of the anesthesiologist (researcher) and the patient. RESULTS: For each group, twenty patients were randomized, which were analyzed at the end of the study. The number of patients presenting absent/mild pain in P+MG was significantly higher than in CG, MG and PG after one hour. After 12 hours, P+MG and PG had more patients with absent/mild pain than CG and MG. At 24 hours postoperatively, all patients in all evaluated groups had no moderate/severe pain. There was no diference in the frequency of patients presenting nausea or vomiting, nor in the scores of the sleep evaluation after surgery in the four groups. CONCLUSION: The combination of magnesium sulfate and pregabalin provided satisfactory analgesia in the first hour after mastectomy with axillary lymphadenectomy. Nevertheless, magnesium sulfate isolated presented no analgesic beneft for the patients, and pregabalin isolated was only slightly effective at the first hour after surgery.

RESUMO JUSTIFICATIVA E OBJETIVOS: Mastectomia com linfadenectomia é uma cirurgia que causa dor moderada ou intensa no pós-operatório imediato. Muitos fármacos adjuvantes, seguros, que promovem boa analgesia e com poucos efeitos adversos têm sido pesquisados. A pregabalina e o sulfato de magnésio são fármacos que promovem analgesia com poucos efeitos adversos. O objetivo deste estudo foi avaliar o efeito analgésico da pregabalina e do sulfato de magnésio no pós-operatório de mastectomia com linfadenectomia axilar. MÉTODOS: Estudo randomizado e duplo-cego envolvendo 80 pacientes submetidas à mastectomia com linfadenectomia axilar sob anestesia geral. As pacientes foram divididas em quatro grupos: Controle (GC, não receberam o fármaco adjuvante proposto); Magnésio+Placebo (GM, receberam sulfato de magnésio durante a anestesia); Pregabalina+Magnésio (GP+M, receberam magnésio adicionado a pregabalina 150 mg antes e 12 h após a cirurgia); e Pregabalina+Placebo (GP, receberam a pregabalina). Todas as pacientes responderam o Self-Report Questionnaire 20 (SRQ-20) para rastrear possível transtorno mental e foram seguidas, monitorando o estado físico 1h, 12h e 24h após a cirurgia, através de anamnese, questionário de dor, consumo de opioides e presença de complicações e/ou eventos adversos como náusea, vômito e sonolência. A randomização foi realizada por meio de envelopes opacos e selados sem o conhecimento do anestesiologista (pesquisador) e do paciente. RESULTADOS: Foram randomizadas 20 pacientes para cada grupo, as quais foram analisadas ao fim do estudo. O número de pacientes apresentando dor ausente/leve no GP+M foi significantemente maior que nos GC, GM e GP após uma hora. Após 12 horas, GP+M e GP apresentaram maior número de pacientes com dor ausente/leve que GC e GM. Em 24 horas do pós-operatório, todos os pacientes de todos os grupos avaliados não apresentaram dor moderada/severa. Não houve diferença na frequência de pacientes apresentando náusea ou vômito, nem nos escores da avaliação do sono após a cirurgia nos quatro grupos. CONCLUSÃO: A associação de sulfato de magnésio e pregabalina causa boa analgesia de mastectomia com linfadenectomia axilar na primeira hora do pós-operatório. No entanto, o uso isolado do sulfato de magnésio não trouxe benefício para analgesia nestas pacientes, assim como a pregabalina sozinha se mostrou pouco efetiva na primeira hora de avaliação.

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

Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain.

This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.

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.

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.