Comparison of therapeutic effects of N-Acetylcysteine with pregabalin in improving the clinical symptoms of painful diabetic neuropathy: a randomized, double-blind clinical trial.

OBJECTIVES: Painful diabetic neuropathy (PDN) is highly prevalent and annoyingly in patients with diabetes. The aim of this study was to investigate the effects of oral N-acetylcysteine (NAC) compared to pregabalin in PDN. METHODS: One hundred two eligible patients with type 2 diabetes and PDN were randomly recievied pregabalin (150 mg/day) or N-Acetylcysteine (NAC) (600 mg/ twice a day) for 8 weeks. Mean pain score, Sleep interference score (SIS), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and also, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study. RESULTS: NAC was well tolerated in all patients. The decrease in mean pain scores and increase in SIS was similar between two groups. More improvement in PGIC and CGIC from the baseline was reported in NAC group. NAC, significantly, decreased serum levels of MDA, and NO, but increased TAC, TTG, and CAT. Pregabalin, significantly, decreased serum levels of MDA, and NO and increased TAC. DISCUSSION: NAC is efficacious in alleviate symptoms of PDN which is probably related to its antioxidant effects. TRIAL REGISTRATION: The research protocol received approval from the Ethics Committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1397.137). The trial registry URL and number in Iranian Registry of Clinical Trials (IRCT): https://www.irct.ir/trial/33313 , IRCT20180814040795N2 (Registration date: 2019-01-21, Retrospectively registered).

[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient's rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

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.

Combination of pregabalin and Amitriptyline in management of chronic idiopathic pain following penile prosthesis implantation: a pilot study.

BACKGROUND: Chronic post-penile prosthesis pain is de novo pain persisting > 2 months post-operatively. This pain is inadequately reported, poorly understood and undermanaged. The purpose of this current pilot study was to improvise a medical approach to alleviate the condition and assess the combination of Pregabalin and Amitriptyline in its management. RESULTS: The study enrolled 9 patients complaining of idiopathic penile, pelvic, or scrotal pain persisting > 2 months after penile prosthesis implantation. Patients were prescribed pregabalin 75mg/12h (escalated after 1 week to 150mg/12h upon demand) and Amitriptyline 25mg once daily for 3 months. The pain was reassessed after 10, 30 and 100 days. The dose of pregabalin required and the side effects of the medication were noted. Findings revealed a significant decrease in pain duration (p = 0.007), frequency (p < 0.001), and intensity (p < 0.001); in glanular (p = 0.008), shaft pain (p = 0.046) but not scrotal (p = 0.112). Moreover, a significant decrease was found in sharp pain (p = 0.003) and pain aggravated by touch (p = 0.008) but not aching pain (p = 0.277). Additionally, significant improvement was reported in QoL (p < 0.001) and dose escalation of pregabalin to 150mg/12h was required in only 1 case (11%). CONCLUSION: The combination of pregabalin and amitriptyline is very effective in the management of chronic idiopathic pain following penile prosthesis implantation. However, due to the ambiguity and lack of reporting of the condition, we recommend a multicentric contribution to acknowledge the condition, and weigh its prevalence accurately, whilst evaluating the efficacy of our approach. This study received ethical approval from Ain Shams University Research Ethics Committee (REC) FWA 000017585, on 04/13/2023 (REC-FMASU@med.asu.edu.eg). TRIAL REGISTRATION: no FMASU R98/2023.

RéSUMé: CONTEXTE: La douleur chronique survenant après l'implantation d'une prothèse pénienne est une douleur de novo qui persiste plus de 2 mois après la chirurgie. Cette douleur est mal rapportée, mal comprise et mal gérée. L'objectif de cette étude pilote était d'improviser une approche médicale pour soulager cette douleur, et d'évaluer l'association de la prégabaline et de l'amitriptyline dans sa prise en charge. RéSULTATS: L'étude a inclut 9 patients se plaignant de douleurs idiopathiques au pénis, au bassin ou au scrotum, persistantes depuis plus de 2 mois après l'implantation d'une prothèse pénienne. Les patients se sont vu prescrire 75 mg/12 h de prégabaline (augmenté après 1 semaine à 150 mg/12 h sur demande) et 25 mg d'amitriptyline une fois par jour, pendant 3 mois. La douleur a été réévaluée après 10, 30 et 100 jours. La dose de prégabaline requise et les effets secondaires du médicament ont été notés. Les résultats ont montré une diminution significative de la durée de la douleur (p = 0,007), de sa fréquence (p < 0,001) et de son intensité (p < 0,001), au niveau du gland (p = 0,008), de la verge (p = 0,046) mais pas du scrotum (p = 0,112). De plus, une diminution significative a été observée en ce qui concerne la douleur vive (p = 0,003) et la douleur aggravée par le toucher (p = 0,008), mais pas la douleur aigüe (p = 0,277). Enfin, une amélioration significative de la qualité de vie (p < 0,001) a été rapportée et l'augmentation de la dose de prégabaline à 150 mg/12 h ne s'est avéré nécessaire que dans 1 cas (11 %). CONCLUSION: L'association de la prégabaline et de l'amitriptyline est très efficace dans la prise en charge de la douleur chronique idiopathique suite à l'implantation d'une prothèse pénienne. Cependant, en raison de l'ambiguïté et de l'absence de déclaration de la maladie, nous recommandons la mise en place d'une contribution multicentrique pour reconnaître la maladie et évaluer sa prévalence avec précision, tout en évaluant l'efficacité de notre approche. Cette étude a reçu l'approbation éthique du Comité d'éthique de la recherche (CER) de l'Université Ain Shams 44 FWA 000017585, le 13/04/2023 (REC46 FMASU@med.asu.edu.eg). N° D'ENREGISTREMENT DE L'ESSAI: FMASU R98/2023.

Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

Modeling an evaluation of the efficacy of the novel neuroanalgesic drug mirogabalin for diabetic peripheral neuropathic pain and postherpetic neuralgia therapy.

Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca2+ channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85% and -8.86%, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca2+ channel neuroanalgesic.

Comparative study on the efficacy of pregabalin versus limaprost in patients with lumbar spinal stenosis: A prospective, randomized controlled trial.

BACKGROUND: Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, quality of life, and sleep, aiming to offer insights for medication selection. METHODS: This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality. RESULTS: After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the two groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI > 5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups. CONCLUSIONS: Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the two groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.

Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.

Efficacy and Safety of Single-Dose Pregabalin in Preoperative Pediatric Sedation.

Introduction: This study aimed to investigate the anxiolytic and sedative effects of a single oral dose of 5 mg/kg pregabalin in pediatric patients undergoing elective surgery. It also assessed potential adverse effects and its impact on bispectral index (BIS) responses. Materials and Methods: This prospective randomized clinical trial enrolled 60 pediatric patients undergoing minor elective surgery. Patients were randomly assigned to receive either oral pregabalin (5 mg/kg) or a placebo one hour before induction of anesthesia. Anxiety levels were assessed using the Visual Analog Scale for Anxiety (VAS-A), and sedation levels were evaluated using the Ramsay Sedation Scale (RSS). Results: Pregabalin premedication significantly reduced preoperative anxiety, as indicated by lower VAS-A scores compared to the control group. Sedation levels, measured using the RSS, were significantly higher in the pregabalin group at various time points post-dose. During intubation, skin incision, and recovery, BIS responses were significantly lower in the pregabalin group. Conclusion: The use of single-dose pregabalin preoperatively in children recorded a significant decrease in anxiety and achieved a state of sedation without an increase in adverse effects.

Pregabalin-Induced Parkinsonism: Case Report and Review of the Literature.

Pregabalin is an anti-epileptic drug approved for the treatment of neuropathic pain and focal-onset seizures. In a few cases, pregabalin was associated with parkinsonism. We present a case of a 48-year-old female who had hypertension and was on losartan 50 mg/daily. Her general practitioner prescribed pregabalin 150 mg/daily for fibromyalgia-related pain. The subject doubled the dosage without medical advice. After 5 days of the increased dosage, she started to experience difficulty and slowness in movement associated with resting tremors. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Secondary parkinsonism was suspected, so pregabalin was discontinued. The subject fully recovered within 7 days. To the authors' knowledge, only 6 cases of pregabalin-induced parkinsonism were reported in the literature. Pregabalin discontinuation was the most common management. All individuals fully recovered after pregabalin withdrawal. The mechanism of pregabalin-induced parkinsonism is not fully understood.

Pregabalina preoperatoria previene las fasciculaciones y mialgias inducidas por succinilcolina: metaanálisis de ensayos aleatorizados / Preoperative pregabalin prevents succinylcholine-induced fasciculations and myalgias: A meta-analysis of randomized trials

La succinilcolina es el bloqueador neuromuscular de referencia para la inducción de secuencia rápida. Sin embargo, su uso se asocia a fasciculaciones y mialgias. Se realizó una revisión sistemática y un metaanálisis. Se incluyeron ensayos clínicos controlados aleatorizados comparando gabapentinoides frente a placebo, para la prevención de fasciculaciones y mialgias inducidas por succinilcolina. Se incluyeron seis estudios clínicos aleatorizados. El número total de pacientes fue de 481, de los cuales 241 se incluyeron en el grupo de intervención y 240 en el grupo de placebo. Los gabapentinoides redujeron la incidencia de mialgia inducida por succinilcolina (RR=0,69; IC95%: 0,56-0,84; p<0,001), que siguió siendo estadísticamente significativa para pregabalina (RR=0,71; IC95%: 0,54-0,93; p=0,013) y gabapentina (RR=0,61; IC95%: 0,45-0,82; p=0,001) por separado. No hubo diferencia entre los grupos en cuanto a fasciculaciones (RR=0,92; IC95%: 0,82-1,03; p=0,148). El uso preoperatorio de gabapentinoides se asocia a una menor incidencia de mialgias inducidas por succinilcolina dentro de las primeras 24horas posteriores al procedimiento. (AU)

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction, however, its use is associated with fasciculations and myalgias. A systematic review and meta-analysis including randomized controlled clinical trials was performed comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included. The total number of patients was 481, of which 241 were in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR=.69; 95%CI: .56-.84; P<.001), which remained statistically significant for pregabalin (RR=.71; 95%CI: .54-.93; P=.013) and gabapentin (RR=.61; 95%CI: .45-.82; P=.001) separately. There was no difference between the groups in fasciculations (RR=.92; 95%CI: .82-1.03; P=.148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24hours after the procedure. (AU)

Effect of Pregabalin Initiation on Diuretic Requirements in Patients with Chronic Heart Failure.

BACKGROUND: Literature on pregabalin use in patients with heart failure is largely limited to patient case reports and cohort studies. OBJECTIVE: To evaluate the effect of pregabalin initiation on diuretic requirements in patients with heart failure. METHODS: A retrospective analysis of patients with heart failure who were started on pregabalin between January 1, 2014 and September 1, 2021 at the Veterans Affairs North Texas Health Care System (VANTHCS). The primary objective was to determine the median change in loop diuretic dose, in furosemide dose equivalents (FDE), six months after pregabalin initiation. RESULTS: Out of 58 patients analyzed, there was no statistically significant difference in the primary outcome (p=0.162). The secondary outcomes were found to be non-statistically significant and there was no correlation between pregabalin dose and outcomes. CONCLUSION: This represents the largest analysis of diuretic dose requirements in heart failure patients after initiation of pregabalin. While there was no difference in the median change of diuretic dose prescribed, pregabalin should still be used with caution.

Pregabalin Adjuventia Helped Risperidone-Induced Extrapyramidal Syndrome and Augmented Antipsychotic Response in an Adolescent with Schizophrenia.

Here, authors report on an interesting case of early-onset of schizophrenia where adjunctive pregabalin alleviated risperidone-induced pseudoparkinsonism, helped with insomnia and agitation and boosted antipsychotic response with great tolerability. We wager that gabapentenoids can be a viable option in the niche of psychopharmacotherapy of schizophrenia in CAP population.

Antineuropathic Pain Management After Orthopedic Surgery: A Systematic Review.

Background: The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids. Objective: This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery. Methods: During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic. Results: Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency. Conclusion: Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.

A comprehensive update on the ADMET considerations for α2δ calcium channel ligand medications for treating restless legs syndrome.

INTRODUCTION: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated. AREAS COVERED: The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options. EXPERT OPINION: α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.

Influence of the calcium voltage-gated channel auxiliary subunit (CACNA2D1) absence on intraocular pressure in mice.

The etiology of elevated intraocular pressure (IOP), a major risk factor for glaucoma (optic nerve atrophy), is poorly understood despite continued efforts. Although the gene variant of CACNA2D1 (encoding α2δ1), a calcium voltage-gated channel auxiliary subunit, has been reported to be associated with primary open-angle glaucoma, and the pharmacological mitigation of α2δ1 activity by pregabalin lowers IOP, the cellular basis for α2δ1 role in the modulation of IOP remains unclear. Our recent findings reveled readily detectable levels of α2δ1 and its ligand thrombospondin in the cytoskeletome fraction of human trabecular meshwork (TM) cells. To understand the direct role of α2δ1 in the modulation of IOP, we evaluated α2δ1 null mice for changes in IOP and found a moderate (∼10%) but significant decrease in IOP compared to littermate wild type control mice. Additionally, to gain cellular insights into α2δ1 antagonist (pregabalin) induced IOP changes, we assessed pregabalin's effects on human TM cell actin cytoskeletal organization and cell adhesive interactions in comparison with a Rho kinase inhibitor (Y27632), a known ocular hypotensive agent. Unlike Y27632, pregabalin did not have overt effects on cell morphology, actin cytoskeletal organization, or cell adhesion in human TM cells. These results reveal a modest but significant decrease in IOP in α2δ1 deficient mice, and this response appears to be not associated with the contractile and cell adhesive characteristics of TM cells based on the findings of pregabalin effects on isolated TM cells. Therefore, the mechanism by which pregabalin lowers IOP remains elusive.

The effect of gabapentin and pregabalin on agitation in dementia: Case series of ten patients.

Neurobehavioral symptoms are difficult to manage in dementia patients. Agitation may negatively impact patients' health and increase the caregiver burden. Pharmacological and non-pharmacological approaches can be adopted to reduce agitation. Recently, positive effects of gabapentinoids have been identified in case reports with promising results and good safety profiles. This observational study was aimed to evaluate the effects of gabapentinoids (gabapentin and pregabalin) on agitation in patients with dementia and to document any adverse effects. This was an observational study consisting of ten patients (six female, four male). The mean age was 85.6years (range: 67-97). Eight of the patients (80%) were diagnosed with Alzheimer's disease, and two were diagnosed with mixed dementia. All patients were using acetylcholinesterase inhibitors and memantine either as a monotherapy or combined. No laboratory abnormalities were identified. The Modified Overt Aggression Scale was used to evaluate agitation. Each medication was started with a minimum dose at bedtime (100mg for gabapentin and 25mg for pregabalin) and gradually increased depending on its effect and adverse effects. The median dose was 366.7mg/d (range: 200-600) for gabapentin and 109.4mg/d (range: 25-300) for pregabalin. Agitation was taken under control within days in nine patients (90%) (three receiving gabapentin and six receiving pregabalin). Sedation was the only documented adverse effect in four patients (40%). One patient's medication was switched from pregabalin to gabapentin because of sedation and pregabalin was discontinued in another one due to inefficacy. Gabapentinoids are well tolerated in the elderly with promising results in agitated patients even at lower doses. Pregabalin could be a useful option in these patients.

In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.