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Journal of Clinical Neuroscience :... Jun 2024A single therapeutic approach is not always successful in the treatment of herpes zoster neuralgia, and the appropriate combination of different treatments deserves...
Clinical efficacy of high-voltage pulsed radiofrequency combined with stellate ganglion block in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm.
OBJECTIVES
A single therapeutic approach is not always successful in the treatment of herpes zoster neuralgia, and the appropriate combination of different treatments deserves further exploration. In this study, we investigated the clinical efficacy of high-voltage long-duration pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm.
METHODS
79 cases of acute zoster neuralgia were grouped premised upon differing therapeutic approaches: standard voltage PRF (group S, the temperature, duration, pulse width, frequency and voltage were set to 42 °C, 300 s, 20 ms, 2 Hz, and 45 V), high-voltage long-duration PRF (group H, parameters of PRF were set to 42 °C, 900 s, 20 ms, 2 Hz, and 90 V, respectively), and high-voltage long-duration PRF combined with SGB (group C, parameter settings for PRF are the same as those for group H). The therapeutic outcomes were assessed utilizing the numeric rating scale (NRS), Pittsburgh sleep quality index (PSQI), and Hamilton anxiety rating scale (HAMA). The incidence of clinically significant postherpetic neuralgia post-treatment had been documented.
RESULTS
Compared to baseline, scores of NRS, PSQI, and HAMA at each time point post-treatment decreased across all groups, and the decrease was more significant in the C group than in the S group. At the later stage of treatment, the consumption of pregabalin and tramadol and the plasma levels of interleukin-6 and galectin-3 in the C group were significantly lower than those in the S group. The incidence of PHN in the C group was significantly lower than in the S group.
CONCLUSIONS
The combination of high-voltage long-duration PRF combined with SGB under dual guidance of ultrasound and C-arm represents a safe, effective, environmentally friendly, and cost-efficient method for treating AZN, significantly improving sleep quality, alleviating anxiety, and reducing the risk of PHN occurrence.
PubMed: 38941917
DOI: 10.1016/j.jocn.2024.06.023 -
BMJ Supportive & Palliative Care Jun 2024Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are...
INTRODUCTION
Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic.
MATERIALS/METHODS
We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events.
RESULTS
For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed.
CONCLUSION
There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future.
PROSPERO REGISTRATION NUMBER
CRD42022361193.
PubMed: 38936970
DOI: 10.1136/spcare-2023-004362 -
Pain Reports Apr 2024Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in... (Review)
Review
Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI -0.13 to 0.32). We could not document differences between TCA and serotonin-noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.
PubMed: 38932764
DOI: 10.1097/PR9.0000000000001138 -
Biomedicines Jun 2024Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function.... (Review)
Review
Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management-namely duloxetine, milnacipran, pregabalin, and amitriptyline-which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.
PubMed: 38927473
DOI: 10.3390/biomedicines12061266 -
Acta Dermato-venereologica Jun 2024This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine... (Comparative Study)
Comparative Study
This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.
Topics: Humans; Retrospective Studies; Pruritus; Female; Male; Tertiary Care Centers; Middle Aged; Treatment Outcome; Amitriptyline; Lidocaine; Ketamine; Pregabalin; Aged; Drug Therapy, Combination; Adult; Antipruritics; Florida; Skin Cream; Administration, Cutaneous; Electronic Health Records
PubMed: 38916180
DOI: 10.2340/actadv.v104.40246 -
BMJ Open Jun 2024Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current...
INTRODUCTION
Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.
METHODS AND ANALYSIS
This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).
ETHICS AND DISSEMINATION
This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.
TRIAL REGISTRATION NUMBER
This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
Topics: Humans; Fibromyalgia; Melatonin; Pregabalin; Double-Blind Method; Cross-Over Studies; Drug Therapy, Combination; Adult; Analgesics; Female; Middle Aged; Pain Management; Randomized Controlled Trials as Topic; Male; Pain Measurement; Chronic Pain; Treatment Outcome
PubMed: 38910006
DOI: 10.1136/bmjopen-2024-087180 -
Spinal Cord Jun 2024Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial.
Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury.
STUDY DESIGN
Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial.
OBJECTIVE
To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control.
SETTING
A total of 7 spinal cord injury rehabilitation units in Spain.
METHODS
A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control.
RESULTS
No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief.
CONCLUSIONS
NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.
PubMed: 38898145
DOI: 10.1038/s41393-024-01006-4 -
The Journal of Neuroscience : the... Jun 2024Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506), are commonly used immunosuppressants for preserving transplanted organs and tissues. However, these...
Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506), are commonly used immunosuppressants for preserving transplanted organs and tissues. However, these drugs can cause severe and persistent pain. GluA2-lacking, calcium-permeable AMPA receptors (CP-AMPARs) are implicated in various neurological disorders, including neuropathic pain. It is unclear whether and how constitutive calcineurin, a Ca/calmodulin protein phosphatase, controls synaptic CP-AMPARs. In this study, we found that blocking CP-AMPARs with IEM-1460 markedly reduced the amplitude of AMPAR-EPSCs in excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2), but not in inhibitory neurons expressing vesicular GABA transporter, in the spinal cord of FK506-treated male and female mice. FK506 treatment also caused an inward rectification in the current-voltage relationship of AMPAR-EPSCs specifically in VGluT2 neurons. Intrathecal injection of IEM-1460 rapidly alleviated pain hypersensitivity in FK506-treated mice. Furthermore, FK506 treatment substantially increased physical interaction of α2δ-1 with GluA1 and GluA2 in the spinal cord and reduced GluA1/GluA2 heteromers in endoplasmic reticulum-enriched fractions of spinal cords. Correspondingly, inhibiting α2δ-1 with pregabalin, genetic knockout, or disrupting α2δ-1-AMPAR interactions with an α2δ-1 C-terminus peptide reversed inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons caused by FK506 treatment. In addition, CK2 inhibition reversed FK506 treatment-induced pain hypersensitivity, α2δ-1 interactions with GluA1 and GluA2, and inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons. Thus, the increased prevalence of synaptic CP-AMPARs in spinal excitatory neurons plays a major role in calcineurin inhibitor-induced pain hypersensitivity. Calcineurin and CK2 antagonistically regulate postsynaptic CP-AMPARs through α2δ-1-mediated GluA1/GluA2 heteromeric assembly in the spinal dorsal horn. Clinically used calcineurin inhibitors can cause severe pain, known as calcineurin inhibitor-induced pain syndrome (CIPS). However, its underlying mechanisms remain elusive. This study shows for the first time that calcineurin inhibition caused cell type-specific expression of synaptic Ca-permeable AMPARs in spinal cord excitatory neurons. Blocking spinal Ca-permeable AMPARs reduced CIPS. Calcineurin inhibition potentiated the α2δ-1 (previously known as a calcium channel subunit) interaction with GluA1 and GluA2 subunits, disrupting their intracellular assembly in the spinal cord. Additionally, inhibiting spinal CK2 diminished α2δ-1-AMPAR interactions and synaptic Ca-permeable AMPARs augmented by calcineurin inhibitors. Thus, calcineurin and CK2 dynamically control AMPAR phenotypes in spinal excitatory neurons through α2δ-1-mediated GluA1/GluA2 assembly. Targeting α2δ-1 and CK2 are effective strategies for treating CIPS.
PubMed: 38886057
DOI: 10.1523/JNEUROSCI.0392-24.2024 -
The Journal of International Medical... Jun 2024Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy.... (Review)
Review
Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.
Topics: Humans; Pregabalin; Rhabdomyolysis; Female; Male; Aged, 80 and over; Analgesics; Creatine Kinase
PubMed: 38879799
DOI: 10.1177/03000605241257776 -
European Journal of Pharmacology Jun 2024Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many...
Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.
PubMed: 38876275
DOI: 10.1016/j.ejphar.2024.176738