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Acta Medica Philippina 2024Phantom limb pain (PLP) is difficult to control, and patients frequently exhibit inadequate relief from medications or encounter unbearable side effects. We present here...
Phantom limb pain (PLP) is difficult to control, and patients frequently exhibit inadequate relief from medications or encounter unbearable side effects. We present here a novel application of erector spinae plane (ESP) block to manage PLP. Our patient is a 23-year-old, college student, diagnosed with high-grade osteosarcoma of the right humerus who underwent a right shoulder disarticulation. He reported PLP despite multimodal analgesia postoperatively. An ESP block using a high-frequency linear probe ultrasound was performed. A G23 spinal needle was advanced in-plane toward the right T3 transverse process. After negative aspiration, 20 mL of therapeutic solution containing bupivacaine 0.25%, lidocaine 1%, epinephrine 5 mcg/ml, and 40 mg methylprednisolone was injected. After the procedure, the patient reported that his PLP went down to NRS 1/10. He consistently reported to have an NRS score of 0-1/10 on succeeding consultations despite discontinuation of opioid and pregabalin. In literature, ESP block has been used as a regional technique for shoulder disarticulation surgery and other neuropathic pain conditions, but no account has shown its use for PLP treatment. The procedure was successfully done to alleviate the upper extremity phantom limb pain, significantly reduce analgesic requirements, and improve tolerance of physical therapy and overall quality of life.
PubMed: 38836080
DOI: 10.47895/amp.v58i9.8821 -
Journal of Pharmaceutical and... Sep 2024Pregabalin (PGB) is a γ-aminobutyric acid (GABA) alkylated analog prescribed to treat neuropathic pain, fibromyalgia, and postherpetic neuralgia. Using analytical,...
Pregabalin (PGB) is a γ-aminobutyric acid (GABA) alkylated analog prescribed to treat neuropathic pain, fibromyalgia, and postherpetic neuralgia. Using analytical, spectroscopic methods and molecular docking and molecular dynamics (MD) simulations, a detailed experimental and theoretical investigation was conducted into the binding process and interactions between PGB and double-stranded fish sperm deoxyribonucleic acid (dsDNA). It was evident from the collected experimental results that PGB binds with ds-DNA. PGB attaches to dsDNA via minor groove binding, as demonstrated by the results of electrochemical studies, UV-Vis absorption spectroscopy, and replacement study with ethidium bromide and Hoechst-32588. PGB's binding constant (K) with dsDNA, as determined by the Benesi-Hildebrand plot, is 2.41×10 ± 0.30 at 298 K. The fluorescence investigation indicates that PGB and dsDNA have a binding stoichiometry (n) of 1.21 ± 0.09. Molecular docking simulations were used in the research to computational determination of the interactions between PGB and dsDNA. The findings demonstrated that minor groove binding was the mechanism by which PGB interacted with dsDNA. Based on the electrochemically responsive PGB-dsDNA biosensor, we developed a technique for low-concentration detection of PGB utilizing differential pulse voltammetry (DPV). The voltammetric analysis of the peak current decrease in the deoxyadenosine oxidation signals resulting from the association between PGB and dsDNA enabled a sensitive estimation of PGB in pH 4.80 acetate buffer. The deoxyguanosine oxidation signals exhibited a linear relationship between 2 and 16 μM PGB. The values for the limit of detection (LOD) and limit of quantitation (LOQ) were 0.57 μM and 1.91 μM, respectively.
Topics: Molecular Docking Simulation; DNA; Pregabalin; Biosensing Techniques; Electrochemical Techniques; Molecular Dynamics Simulation; Animals; Spectrophotometry, Ultraviolet; Male; Limit of Detection; Spermatozoa; Spectrometry, Fluorescence; Fishes
PubMed: 38823224
DOI: 10.1016/j.jpba.2024.116261 -
International Journal of Medical... 2024This study investigated the effects of pregabalin on microglial differentiation in rats with neuropathic pain (NP) induced by sciatic nerve ligation and transection....
This study investigated the effects of pregabalin on microglial differentiation in rats with neuropathic pain (NP) induced by sciatic nerve ligation and transection. After confirming NP, the rats were randomly allocated to either a pregabalin or control group. The pregabalin group received intraperitoneal injections of 10 mg/kg pregabalin, while the control group received an equivalent volume of normal saline following surgery. On postoperative day 28, neuronal damage, microglial activity, and microglial differentiation were assessed. The pregabalin group exhibited significantly less neuronal damage compared to the control group, along with a significant decrease in activated microglial expression in both the brain and spinal cord. Pregabalin treatment also significantly altered the microglial phenotype expression, with a decrease in the M1 phenotype percentage and an increase in the M2 phenotype percentage in both the brain (M1 phenotype: 43.52 ± 12.16% and 18.00 ± 8.57% in the control and pregabalin groups, respectively; difference: 27.26 [15.18-42.10], p = 0.002; M2 phenotype: 16.88 ± 6.47% and 39.63 ± 5.82% in the control and pregabalin groups, respectively; difference 22.04 [17.17-32.70], p < 0.001) and the spinal cord ipsilateral to nerve injury (M1 phenotype: 44.35 ± 12.12% and 13.78 ± 5.39% in the control and pregabalin groups, respectively; difference 30.46 [21.73-44.45], p < 0.001; M2 phenotype: 7.64 ± 3.91% and 33.66 ± 7.95% in the control and pregabalin groups, respectively; difference 27.41 [21.21-36.30], p < 0.001). Overall, pregabalin treatment significantly decreased the microglial M1 phenotype while increasing the microglial M2 phenotype in NP rats.
Topics: Animals; Pregabalin; Microglia; Neuralgia; Rats; Cell Differentiation; Male; Spinal Cord; Disease Models, Animal; Analgesics; Sciatic Nerve; Rats, Sprague-Dawley; Humans; Brain
PubMed: 38818478
DOI: 10.7150/ijms.96236 -
International Clinical... May 2024This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety...
This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety disorder (GAD) in adult patients. We selected randomized controlled trials on various medications used to treat GAD in adult patients. An existing systematic literature review (Kong et al., 2020) was used to identify relevant studies published before 2020. Outcomes of remission and discontinuation due to adverse events (AEs) were analyzed, following a random-effects network meta-analysis approach. Of 25 identified studies, 20 and 22 studies were included in the network meta-analysis for studying the remission and discontinuation (due to AEs) outcomes, respectively. A statistically significant difference in the remission rate was observed between agomelatine and pregabalin [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.19-4.21]. For the other comparators, the results were nonsignificant; however, all the point estimates were in favor of agomelatine. Similarly, for discontinuation because of AEs, the point estimates leaned consistently toward agomelatine suggesting its higher tolerability. The probabilities of agomelatine having the highest remission rate and lowest discontinuation (due to AEs) rate were 67% and 68%, respectively. Based on its demonstrated effectiveness and tolerability, agomelatine can be considered as a drug of choice for the treatment of GAD.
PubMed: 38804215
DOI: 10.1097/YIC.0000000000000551 -
BMJ Neurology Open 2024Bronchial artery embolization (BAE) is the established first-line treatment for patients presenting with massive haemoptysis, a life-threatening condition that can occur...
BACKGROUND
Bronchial artery embolization (BAE) is the established first-line treatment for patients presenting with massive haemoptysis, a life-threatening condition that can occur because of numerous underlying diseases. BAE is a relatively safe procedure with control of haemorrhage achieved in 77%-90% of cases and rare occurrence of complications. Spinal cord infarction is one such rare complication, which can have severe implications in terms of morbidity.
CASE PRESENTATIONS
We present a case of a 70-year-old man who developed paraplegia with loss of pain and temperature sensation as well as sphincteric involvement following BAE for hemoptysis. MRI of the spine was suggestive of an ischaemic event involving anterolateral spinal cord segment T4-T6, so a diagnosis of anterior spinal artery syndrome post BAE was made. The patient was given corticosteroids, dual antiplatelet medications, pregabalin, supportive management and regular physiotherapy. Follow-up of the patient at 3 and 6 months failed to show any significant improvement in neurological function, although the patient did not report problem of significant hemoptysis afterward.
CONCLUSION
Spinal cord infarct is a rare and disabling complication of BAE despite it being a safe procedure with good long-term outcomes. Detailed knowledge about the anatomy of bronchial arteries and spinal arteries with detailed preprocedure investigations may lower the risk of this disabling complication.
PubMed: 38800071
DOI: 10.1136/bmjno-2024-000684 -
Pharmacological Reports : PR May 2024Among clinically highly efficient antiseizure medications (ASMs) there are modifiers of the presynaptic release machinery. Of them, levetiracetam and brivaracetam show a... (Review)
Review
Among clinically highly efficient antiseizure medications (ASMs) there are modifiers of the presynaptic release machinery. Of them, levetiracetam and brivaracetam show a high affinity to the synaptic vesicle protein type 2 A (SV2A), whereas pregabalin and gabapentin are selective ligands for the α2δ1 subunits of the voltage-gated calcium channels. In this paper, we present recent progress in understanding the significance of presynaptic release machinery in the neurochemical mechanisms of epilepsy and ASMs. Furthermore, we discuss whether the knowledge of the basic mechanisms of the presynaptically acting ASMs might help establish a rational polytherapy for drug-resistant epilepsy.
PubMed: 38776036
DOI: 10.1007/s43440-024-00603-7 -
Scientific Reports May 2024Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence... (Randomized Controlled Trial)
Randomized Controlled Trial
Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.
Topics: Humans; Fibromyalgia; Hyperbaric Oxygenation; Female; Male; Adult; Middle Aged; Child Abuse, Sexual; Prospective Studies; Duloxetine Hydrochloride; Pregabalin; Treatment Outcome; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Analgesics
PubMed: 38773296
DOI: 10.1038/s41598-024-62161-5 -
Epilepsy Research Jul 2024Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during...
BACKGROUND
Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior.
METHODS
Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control.
RESULTS
Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286).
CONCLUSIONS
Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.
Topics: Humans; Anticonvulsants; Self-Injurious Behavior; United States; United States Food and Drug Administration; Male; Female; Adverse Drug Reaction Reporting Systems; Adult; Adolescent; Middle Aged; Suicide; Young Adult; Databases, Factual; Pharmacovigilance; Child; Aged
PubMed: 38761467
DOI: 10.1016/j.eplepsyres.2024.107382 -
Acta Dermato-venereologica May 2024Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding...
Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding the therapeutic effects of antipruritics. This study proposes an age-related alloknesis mouse model for an evaluation system for such cases, and aimed to investigate the effectiveness and mechanisms of action of several drugs commonly used as antipruritics in Japan, utilizing this model. Mice 69-80 weeks old were used as aged mice, and the level of mechanical alloknesis was counted as the number of scratching behaviours in response to innocuous stimuli. Bepotastine, neurotropin, pregabalin, baricitinib, and abrocitinib were used as antipruritics, and yohimbine and methysergide as inhibitors of the descending inhibitory pathway. The findings suggest that mechanical alloknesis in aged mice is a suitable animal model for assessing pruritus in the elderly without xerosis, and pregabalin, neurotropin, baricitinib, and abrocitinib may be effective antipruritics in the elderly through activating both the noradrenergic and serotonergic descending inhibitory pathways. These findings may be useful for the selection of antipruritics for pruritus in the elderly without skin lesions or dryness.
Topics: Animals; Pruritus; Disease Models, Animal; Antipruritics; Chronic Disease; Behavior, Animal; Mice; Age Factors; Male; Sulfonamides; Pregabalin; Pyrazoles; Purines; Aging; Azetidines
PubMed: 38751178
DOI: 10.2340/actadv.v104.39950 -
MedRxiv : the Preprint Server For... Jun 2024In a genome-wide association study (GWAS) of 685,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries and across diverse and admixed...
Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies.
In a genome-wide association study (GWAS) of 685,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries and across diverse and admixed ancestries, we identify 697 independent associations at 636 genetic loci, 293 of which are novel. Using fine-mapping and functional genomic datasets, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. Leveraging new single-cell gene expression data, we conducted a causal neural cell type enrichment analysis that implicated excitatory and inhibitory midbrain and forebrain neurons, peptidergic neurons, and medium spiny neurons in MD. Critically, our findings are enriched for the targets of antidepressants and provide potential antidepressant repurposing opportunities (e.g., pregabalin and modafinil). Polygenic scores (PGS) from European ancestries explained up to 5.7% of the variance in liability to MD in European samples and PGS trained using either European or multi-ancestry data significantly predicted case control status across all four diverse ancestries. These findings represent a major advance in our understanding of MD across global populations. We provide evidence that MD GWAS reveals known and novel biological targets that may be used to target and develop pharmacotherapies addressing the considerable unmet need for effective treatment.
PubMed: 38746223
DOI: 10.1101/2024.04.29.24306535