Metabotropic Glutamate Receptor 4 (mGlu4) Positive Allosteric Modulators Lack Efficacy in Rat and Marmoset Models of L-DOPA-Induced Dyskinesia.

Background: Increased activity across corticostriatal glutamatergic synapses may contribute to L-DOPA-induced dyskinesia in Parkinson's disease. Given the weak efficacy and side-effect profile of amantadine, alternative strategies to reduce glutamate transmission are being investigated. Metabotropic glutamate receptor 4 (mGlu4) is a promising target since its activation would reduce glutamate release. Objective: We hypothesized that two mGlu4 positive allosteric modulators, Lu AF21934 ((1 S,2 R)-N1-(3,4-dichlorophenyl)cyclohexane-1,2-dicarboxamide) and ADX88178 (5-Methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine), would provide relief in rat and primate models of L-DOPA-induced dyskinesia. Methods: The ability of Lu AF21934 or ADX88178 to reverse pre-established dyskinesia was examined in L-DOPA-primed 6-hydroxydopamine-lesioned rats expressing abnormal involuntary movements (AIMs) or in 1-methyl-4-phenyl,1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets expressing L-DOPA-induced dyskinesia. Additionally, the ability of Lu AF21934 to prevent the development of de novo L-DOPA-induced AIMs was explored in the 6-hydroxydopamine-lesioned rats. Results: Neither Lu AF21934 (10 or 30 mg/kg p.o.) nor ADX88178 (10 or 30 mg/kg p.o.) reduced pre-established AIMs in 6-hydroxydopamine-lesioned rats. Similarly, in L-DOPA-primed common marmosets, no reduction in established dyskinesia was observed with Lu AF21934 (3 or 10 mg/kg p.o.). Conversely, amantadine significantly reduced (>40%) the expression of dyskinesia in both models. Lu AF21934 also failed to suppress the development of AIMs in 6-hydroxydopamine-lesioned rats. Conclusions: This study found no benefit of mGlu4 positive allosteric modulators in tackling L-DOPA-induced dyskinesia. These findings are concordant with the recent failure of foliglurax in phase II clinical trials supporting the predictive validity of these pre-clinical dyskinesia models, while raising further doubt on the anti-dyskinetic potential of mGlu4 positive allosteric modulators.

An organic O donor for biological hydroxylation reactions.

All biological hydroxylation reactions are thought to derive the oxygen atom from one of three inorganic oxygen donors, O2, H2O2, or H2O. Here, we have identified the organic compound prephenate as the oxygen donor for the three hydroxylation steps of the O2-independent biosynthetic pathway of ubiquinone, a widely distributed lipid coenzyme. Prephenate is an intermediate in the aromatic amino acid pathway and genetic experiments showed that it is essential for ubiquinone biosynthesis in Escherichia coli under anaerobic conditions. Metabolic labeling experiments with 18O-shikimate, a precursor of prephenate, demonstrated the incorporation of 18O atoms into ubiquinone. The role of specific iron-sulfur enzymes belonging to the widespread U32 protein family is discussed. Prephenate-dependent hydroxylation reactions represent a unique biochemical strategy for adaptation to anaerobic environments.

Gabapentin for Pain in Pediatric Palliative Care.

OBJECTIVE: Gabapentin is commonly used to treat pain in children receiving pediatric palliative care. This study describes the real-world use of gabapentin and the associated benefits and adverse effects/events (AEs). METHODS: A prospective, multicenter cohort of standardized data collection after a clinical decision was made to use gabapentin for managing neuropathic or nociplastic pain in children attended on by a pediatric palliative care service. It was conducted across 11 sites in seven countries including hospital, inpatient, and outpatient services. Clinical outcomes were graded using pain scales validated for age and cognitive ability and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) at baseline, 14 days, 28 days, six weeks and 12 weeks after initiation of gabapentin. Ad-hoc safety reporting continued throughout the study. RESULTS: Data were collected from 127 children with a median age of 4.7 years (IQR 0.1-17.9); 61% had a neurological disorder, 21% advanced cancer and the cohort had a high level of disability (Lansky/Karnofsky performance score 37.1). Gabapentin was prescribed at standard pediatric doses. On average, 76% of children had a reduction in pain and 42% experienced a potential AE. The mean pain score decreased from 6.0 (SD 2.6) at baseline to 3.3 (SD 2.4) at 14 days and 1.8 (SD 1.8) after 12-weeks of gabapentin therapy. Ten percent had increased pain at each time point. AEs did not increase when individual changes over time were accounted for except for somnolence (7%). Serious AEs attributable to gabapentin were possible or probable in 3% of children. CONCLUSIONS: Gabapentin prescribed at standard doses for advanced cancer and severe neurological injury in children under a pediatric palliative care service was associated with generally improved pain intensity at previously described levels of adverse effects.

Comparative analysis of diisononyl phthalate and di(isononyl)cyclohexane-1,2 dicarboxylate plasticizers in regulation of lipid metabolism in 3T3-L1 cells.

Diisononyl phthalate (DINP) and di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) are plasticizers introduced to replace previously used phthalate plasticizers in polymeric products. Exposure to DINP and DINCH has been shown to impact lipid metabolism. However, there are limited studies that address the mechanisms of toxicity of these two plasticizers. Here, a comparative toxicity analysis has been performed to evaluate the impacts of DINP and DINCH on 3T3-L1 cells. The preadipocyte 3T3-L1 cells were exposed to 1, 10, and 100 µM of DINP or DINCH for 10 days and assessed for lipid accumulation, gene expression, and protein analysis. Lipid staining showed that higher concentrations of DINP and DINCH can induce adipogenesis. The gene expression analysis demonstrated that both DINP and DINCH could alter the expression of lipid-related genes involved in adipogenesis. DINP and DINCH upregulated Pparγ, Pparα, C/EBPα Fabp4, and Fabp5, while both compounds significantly downregulated Fasn and Gata2. Protein analysis showed that both DINP and DINCH repressed the expression of FASN. Additionally, we analyzed an independent transcriptome dataset encompassing temporal data on lipid differentiation within 3T3-L1 cells. Subsequently, we derived a gene set that accurately portrays significant pathways involved in lipid differentiation, which we subsequently subjected to experimental validation through quantitative polymerase chain reaction. In addition, we extended our analysis to encompass a thorough assessment of the expression profiles of this identical gene set across 40 discrete transcriptome datasets that have linked to diverse pathological conditions to foreseen any potential association with DINP and DINCH exposure. Comparative analysis indicated that DINP could be more effective in regulating lipid metabolism.

Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2.

Niacin, an age-old lipid-lowering drug, acts through the hydroxycarboxylic acid receptor 2 (HCAR2), a G-protein-coupled receptor (GPCR). Yet, its use is hindered by side effects like skin flushing. To address this, specific HCAR2 agonists, like MK-6892 and GSK256073, with fewer adverse effects have been created. However, the activation mechanism of HCAR2 by niacin and these new agonists is not well understood. Here, we present three cryoelectron microscopy structures of Gi-coupled HCAR2 bound to niacin, MK-6892, and GSK256073. Our findings show that different ligands induce varying binding pockets in HCAR2, influenced by aromatic amino acid clusters (W91ECL1, H1614.59, W1885.38, H1895.39, and F1935.43) from receptors ECL1, TM4, and TM5. Additionally, conserved residues R1113.36 and Y2847.43, unique to the HCA receptor family, likely initiate activation signal propagation in HCAR2. This study provides insights into ligand recognition, receptor activation, and G protein coupling mediated by HCAR2, laying the groundwork for developing HCAR2-targeted drugs.

Gabapentin and oral antidepressants for chronic pruritus: a prospective cohort study evaluating efficacy and side effects in daily dermatological practice.

BACKGROUND: Chronic pruritus is frequently seen in daily dermatological practice and is associated with marked impact on quality of life. Research on the use of gabapentin and oral antidepressants in daily dermatological practice is scarce. OBJECTIVE: To evaluate the efficacy and safety of gabapentin and oral antidepressants in patients with chronic pruritus in daily clinical practice. METHODS: A prospective observational single-center cohort study was conducted including adult patients with chronic pruritus and an indication for systemic treatment between June 2016 and May 2019. RESULTS: Systemic treatment with gabapentin and/or antidepressants was initiated in 31 patients with severe chronic pruritus (median average pruritus NRS score 7.0), in which most cases no underlying origin was identified (83.9%). In patients treated with gabapentin 900-1800 mg/day (N = 25), median average pruritus NRS decreased to 5.5 (IQR 3.0) after 4 weeks and remained stable up to 24 weeks of treatment. Efficacy of antidepressants was variable, with the highest response after initiation of amitriptyline, nortriptyline, and mirtazapine. Side effects were frequently observed in both gabapentin and antidepressant treatments; however, were mostly mild and temporary. LIMITATIONS: This was a single-site observational study, with limited sample size. CONCLUSION: Treatment with gabapentin and antidepressants should be considered in patients with chronic pruritus unresponsive to conventional treatment.

Comparative Descriptive Analysis of Physician Versus Patient-Directed Gabapentin Usage In Chronic Pain - A Preliminary Report.

BACKGROUND: Gabapentin is one of the most common medications employed in Pain Medicine, specifically targeting the management of neuropathic pain. We are most familiar with the incremental dosing strategy where a ceiling dose is eventually attained guided by efficacy and patient tolerance, after which a fixed dosing regimen is prescribed. We propose that autonomous short-term dose variations per patient could have rapid clinically significant effects in the management of chronic pain. OBJECTIVES: This study examines the frequency at which patients take gabapentin on a fixed vs variable schedule and how the pattern of gabapentin use correlates with efficacy, side effects, and patient satisfaction. STUDY DESIGN: Single institution, cross-sectional observational survey study with data collection performed over 2 phases as a pilot for proof of concept. SETTING: Remote contact via telephone with researchers calling from a quiet, private location within the hospital complex conducive for confidential conversation. METHODS: Patients recently prescribed gabapentin were queried on the patterns of use and self-perceived efficacy, satisfaction, and side effects in accordance to a standardized oral script. Patients selected met the criteria of being new patients freshly prescribed gabapentin who have been consistently on the medication for at least a month, while having chronic pain symptoms for over 3 months. Responses were collected in the form of a 5-point Likert scale. Statistical analyses were performed using GraphPad Prism. RESULTS: Of the 222 patients, 92 patients agreed to participate in the survey for a response rate of 41.4. Of these, 51% had terminated the medication for various reasons. Of the patients still taking gabapentin, 73% were on a fixed schedule, while 27% were on a variable dosing schedule. Variable dosing cohort reported better efficacy (P = 0.027) and satisfaction (P = 0.036), while the side-effect profile between the 2 groups was similar. LIMITATIONS: The study is limited by its nature of being a pilot, single-institution study performed on a relatively small sample size. None of the patients we surveyed had been given the autonomy to adjust gabapentin doses by their providers and this could significantly reduce the proportion of patients who would be encouraged to run a variable dosing regimen. CONCLUSIONS: This pilot study suggests that a significant portion of patients choose to administer variable doses of gabapentin and associate this with better efficacy and satisfaction. A larger study is needed to confirm this supposition. Based upon this pilot study, the variable dosing option may be an option for improved therapeutic efficacy or as an alternative to those whose lifestyles do not allow for fixed dosing regimens. Discussion of the risks of gabapentin, including respiratory depression, and clear dosage parameters of use, would need to be outlined when considering a variable dose regimen.

Effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients in southwestern Iran: a randomized clinical trial.

BACKGROUND: Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the current study aims to determine the effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients. METHODS: This 12-week, randomized, and parallel-group trial was conducted to compare the efficacy of oral clonidine and gabapentin with gabapentin alone in diabetic patients in southwest Iran during the first half of 2021. Thirty patients with type 2 diabetes with peripheral neuropathy as assessed by a visual analog scale (VAS) and divided into two groups of 15 patients, treated for up to three months. The data were analyzed using SPSS-21 software. In order to report the results, descriptive indices, independent t-test, one-way analysis of covariance (ANCOVA) and analysis of variance with repeated measures were used. RESULTS: The mean and standard deviation of the age of the participants in the clonidine + gabapentin group was equal to 50.20 ± 7.44, and in the gabapentin group was equal to 50.47 ± 7.57 (t = 0.10, P-value = 0.923). This research showed a significant difference between the clonidine + gabapentin group and with gabapentin group in terms of neuropathic pain and the severity of neuropathic pain (P < 0.001). CONCLUSIONS: According to this research results, clonidine + gabapentin can reduce neuropathic pain and the severity of neuropathic pain in diabetic patients. Therefore, it is recommended that healthcare professionals with diabetes expertise prescribe these medications to reduce neuropathic pain and its severity. TRIAL REGISTRATION: This study was registered in the Iranian Clinical Trials System with the ID (IRCT20211106052983N1) on 14/01/2022.

ß-Peptides incorporating polyhydroxylated cyclohexane ß-amino acid: synthesis and conformational study.

We describe the synthesis of trihydroxylated cyclohexane ß-amino acids from (-)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans-2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of trans-2-aminocyclohexanecarboxylic acid. This means that the high degree of substitution of the cyclohexane ring of the new residue is compatible with the adoption of a stable helical secondary structure and opens opportunities for the design of more elaborate peptidic foldamers with oriented polar substituents at selected positions of the cycloalkane residues.

Natural Oil Lure Outperforms Trimedlure in Capturing Males of the Mediterranean Fruit Fly, Ceratitis capitata (Diptera: Tephritidae).

Females of certain tephritid fruit fly species (Diptera: Tephritidae) pose an enormous agricultural threat, as they oviposit in commercially important fruits and vegetables. Trapping networks are often operated in fruit fly-free areas to detect incipient infestations. Trapping relies largely on male attractants, so-called male lures, with trimedlure (TML) being used to detect invasive Ceratitis spp. Operating large-scale surveillance programs incurs substantial costs for both supplies and labor, and the problem is exacerbated by the fact that trimedlure (as well as other male lures) is effective for relatively short intervals in the field (6-8 weeks). Because frequent servicing increases costs, there is considerable interest in modifying existing lures or developing new formulations to extend their effective field longevity. Here, we present results of a field study in Hawaii on a wild population of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), that compared male captures in traps baited with (i) fresh liquid TML, (ii) TML plugs, (iii) a novel controlled-release TML sachet, and (iv) a novel natural oil blend dispensed from a sachet. Catch was recorded weekly for 12 weeks and then at 16 and 20 weeks, with 12 traps deployed per treatment. The natural oil formulation, which contains the natural plant product α-copaene, was as effective as the fresh liquid TML even after weathering for 20 weeks. Future work will focus on developing a dispenser for this formulation that is compatible with standard trap design and deployment.

Orthosteric ligand selectivity and allosteric probe dependence at Hydroxycarboxylic acid receptor HCAR2.

Hydroxycarboxylic acid receptor 2 (HCAR2), a member of Class A G-protein-coupled receptor (GPCR) family, plays a pivotal role in anti-lipolytic and anti-inflammatory effects, establishing it as a significant therapeutic target for treating dyslipidemia and inflammatory diseases. However, the mechanism underlying the signaling of HCAR2 induced by various types of ligands remains elusive. In this study, we elucidate the cryo-electron microscopy (cryo-EM) structure of Gi-coupled HCAR2 in complex with a selective agonist, MK-6892, resolved to a resolution of 2.60 Å. Our structural analysis reveals that MK-6892 occupies not only the orthosteric binding pocket (OBP) but also an extended binding pocket (EBP) within HCAR2. Pharmacological assays conducted in this study demonstrate that the OBP is a critical determinant for ligand selectivity among the HCARs subfamily. Moreover, we investigate the pharmacological properties of the allosteric modulator compound 9n, revealing its probe-dependent behavior on HCAR2 in response to varying orthosteric agonists. Collectively, our findings provide invaluable structural insights that contribute to a deeper understanding of the regulatory mechanisms governing HCAR2 signaling transduction mediated by both orthosteric and allosteric ligands.

Abuse and addiction in gabapentinoid drug users for neuropathic pain.

OBJECTIVE: Gabapentinoids are gamma-aminobutyric acid analogue agents used in the treatment of neuropathic pain. They are increasingly being abused to achieve euphoric and dissociative effects. This study aimed to determine drug misuse/abuse and related factors in patients who used gabapentinoids for neuropathic pain. PATIENTS AND METHODS: This study included 140 patients over the age of 18. Patients were excluded from the study if they had aphasia, dementia, or diseases that led to aphasia or cooperative and cognitive dysfunction. They were also excluded if they lacked sufficient information about how long or at what dosage they had been using the drug. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety states. The patients' levels of drug abuse were determined according to the definitions provided in the terminology for misuse, abuse, and related events. RESULTS: The mean age of the patients was 56.78 ± 14.45 years, and 52.1% of them were females. While 57.9% of the patients used pregabalin, 42.1% of the patients used gabapentin. For the median (min-max) of the dataset, the pregabalin dose was 300 (50-600) mg/day, and the gabapentin dose was 900 (300-2,400) mg/day. Abuse was present in 17.9% of the patients. Risk factors for gabapentinoid abuse were smoking, alcohol, and antidepressant use, anxiety and depression, living alone, and drug dose and duration of use. CONCLUSIONS: Before prescribing drugs and managing the treatment process in a controlled manner, questioning patients about their risk factors can reduce the rate of abuse.

Elsholblanosides A-D, Four New Oleuropeic Acid Derivatives Isolated from Elsholtzia blanda and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.

Phytochemical investigation on the aerial parts of Elsholtzia blanda Benth. afforded four new oleuropeic acid derivatives (1-4), named as elsholblanosides A-D, respectively, together with 11 known compounds (5-15). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR, and ECD spectra. Compounds 1-4 and 14 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with their IC50 values ranging from 23.2 to 86.33 µM, compared to that of the positive control compound, dexamethasone, IC50 value of 16.9 µM.

Migration of di(2-ethylhexyl) phthalate, diisononylcyclohexane-1,2-dicarboxylate and di(2-ethylhexyl) terephthalate from transfusion medical devices in labile blood products: A comparative study.

BACKGROUND AND OBJECTIVES: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is a widely used material for medical transfusion devices. Not covalently bound to PVC, DEHP can migrate into blood products during storage. Recognized as an endocrine disruptor and raising concerns about its potential carcinogenicity and reprotoxicity, DEHP is gradually being withdrawn from the medical device market. Therefore, the use of alternative plasticizers, such as diisononylcyclohexane-1,2-dicarboxylate (DINCH) and di(2-ethylhexyl) terephthalate (DEHT), as potential candidates for the replacement of DEHP in medical transfusion devices has been investigated. The purpose of this study was to evaluate the quantity of PVC-plasticizers in the blood components according to their preparation, storage conditions and in function of the plasticizer. MATERIALS AND METHODS: Whole blood was collected, and labile blood products (LBPs) were prepared by the buffy-coat method with a PVC blood bag plasticized either with DEHP, DINCH or DEHT. DINCH and DEHT equivalent concentrations were quantified in LBPs by liquid chromatography-tandem mass spectrometry or coupled with UV and compared to DEHP equivalent concentrations. RESULTS: The plasticizer equivalent concentration to which a patient is exposed during a transfusion depends on the preparation of LBPs as well as their storage conditions, that is, temperature and storage time. At day 1, for all LBPs, the migration of DEHP is 5.0 and 8.5 times greater than DINCH and DEHT, respectively. At the end of the 49 days storage period, the DEHP equivalent concentration in red blood cells concentrate is statistically higher when compared to DINCH and DEHT, with maximal values of 1.85, 1.13 and 0.86 µg/dm2 /mL, respectively. CONCLUSION: In addition to lower toxicity, transfused patients using PVC-DEHT or PVC-DINCH blood bags are less exposed to plasticizers than using PVC-DEHP bags with a ranging exposure reduction from 38.9% to 87.3%, due to lower leachability into blood components.

Prophylactic gabapentin during head and neck cancer therapy: a systematic review and meta-analysis.

PURPOSE: This review was designed to compile the currently available evidence on the prophylactic use of gabapentin in the head and neck cancer patient population. METHODS: A systematic search was conducted of PubMed, Web of Science, and Google Scholar to identify articles related to the use of prophylactic gabapentin in patients undergoing head and neck cancer therapy. Candidate studies were screened for inclusion and a subsequent bias assessment was conducted by multiple reviewers. Meta-analysis was conducted in cases in which the studies used compatible outcome measures. RESULTS: Ten studies were identified that met the inclusion criteria and were assessed for bias. Among the four small studies that examined pain prevention, 2 were positive and 2 were inconclusive. Three of the four studies examiniRDng opioid use noted less need for opioids in the treatment arm. Meta-analysis of the pertinent studies showed no difference in feeding tube placement (RD = 0.64%, 95%CI: (- 25.8%, 27.1%), p = 0.962) but substantially less weight loss among those in the treatment arm (p = 0.047). CONCLUSION: Prophylactic gabapentin appears to be a promising treatment option for preventing pain, reducing opioids, and reducing weight loss in patients undergoing head and neck cancer therapy. However, the studies on the treatment to date are small and several have a substantial risk of bias.

The safety and efficacy of gabapentinoids in the management of neuropathic pain: a systematic review with meta-analysis of randomised controlled trials.

BACKGROUND: There are increasing concerns regarding the abusive potential of gabapentinoids putting at risk patients with neuropathic pain requiring long-term pain management. The evidence to support this is rather inconcusive. AIM: This systematic review aimed to evaluate the safety and efficacy of gabapentinoids in the management of neuropathic pain with a focus on randomised controlled trials (RCTs) and categorising the side effects according to the body systems they were affecting. METHOD: Searches were conducted in MEDLINE (PubMed), EMBASE, Web of Science, PsycoINFO, and CINAHL (EBSCO), and included RCTs to identify and critically appraise studies investigating safety and therapeutic effects of gabapentionoids in adults with neuropathic pain. Data extraction was conducted using an established Cochrane form and the risk-of-bias tool was used in the assessment of quality. RESULTS: 50 studies (12,398 participants) were included. The majority of adverse events pertained to the nervous system (7 effects) or psychiatric (3 effects) disorders. There were more adverse effects reported with pregabalin (36 effects) than with gabapentin (22 effects). Six pregabalin studies reported euphoria as a side effect, while no studies reported euphoria with gabapentin. This was the only side effect that may correlate with addictive potential. Gabapentioids were reported to significantly reduce pain compared to placebo. CONCLUSION: Despite RCTs documenting the adverse events of gabapentionoids on the nervous system, there was no evidence of gabapentinoid use leading to addiction, suggesting an urgent need to design studies investigating their abusive potential.

The Efficacy of Gabapentin + Dexamethasone for Postoperative Analgesia Following Septoplasty: A Prospective Randomized Placebo-Controlled Trial.

AIMS: This study aimed to compare the efficacy of gabapentin, dexamethasone, and gabapentin + dexamethasone for pain control after septoplasty. MATERIALS AND METHODS: This prospective randomized trial included 120 patients that underwent septoplasty and were randomly divided into 4 groups: group G (preoperative gabapentin 600 mg p.o.); group D (intraoperative dexamethasone 8 mg i.v.); group GD (preoperative gabapentin 600 mg p.o. + intraoperative dexamethasone 8 mg i.v.); group C (placebo control). RESULTS: The median VAS score was significantly lower in groups G and GD at 1, 2, 4, 6, 12, and 24 hours postsurgery than in group C (P < .008 for all). The median VAS score was significantly lower in group D than in group C at 1, 2, and 4 hours postsurgery (P < .008 for all). There weren't any significant differences in the VAS score between groups D, G, and GD at any time point. Groups G, D, and GD had a significantly lower frequency of rescue analgesic use than group C; however, there were no differences between groups G, GD, and C (P < .001 and P = .108, respectively). CONCLUSION: Gabapentin, dexamethasone, and gabapentin + dexamethasone are equally more effective analgesics during the first 4 hours postsurgery than placebo. The addition of dexamethasone to gabapentin does not provide extra analgesia. Both gabapentin and gabapentin + dexamethasone have a more prolonged analgesic effect than dexamethasone alone.

Misuse of gabapentinoids (pregabalin and gabapentin) in patients with neuropathic pain related to spinal cord injury.

OBJECTIVE: To investigate the misuse of gabapentinoids (pregabalin and gabapentin) in patients with neuropathic pain related to spinal cord injury. STUDY DESIGN: Cross-sectional study. SETTING: Outpatient clinic in a physical therapy and rehabilitation hospital. PARTICIPANTS: 127 patients, aged 18-70 years, who had neuropathic pain related to spinal cord injury (SCI) and disease duration of at least 12 months. OUTCOME MEASURES: Gabapentinoid use disorder of the patients was determined based on the DSM-5 diagnostic criteria for substance-related disorders. Patients were divided into 2 groups as those with drug misuse and those without drug misuse. Demographic and clinical information of the patients were compared between the groups. Factors associated with drug misuse were analyzed. RESULTS: The misuse rate was 81.9% in patients using pregabalin and 69.69% in patients using gabapentin. Duration of disease and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were statistically significantly higher in the drug misuse group. A statistically significant difference was found between the groups in terms of marital status, education and income level, and smoking and alcohol use. A statistically significant relationship was observed between drug misuse and duration of disease and LANSS score. CONCLUSION: Misuse of gabapentinoids is prevalent in patients with neuropathic pain related to spinal cord injury. The duration of disease and the severity of NP are associated with misuse. Clinicians should exercise caution when prescribing gabapentinoids to patients with SCI.