Pregabalin and Gabapentin in Patients with Spinal Cord Injury-Related Neuropathic Pain: A Network Meta-Analysis.
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ABSTRACT: Introduction
This study was performed to explore the efficacy and safety of pregabalin and gabapentin in patients with spinal cord injury (SCI)-induced neuropathic pain to determine which treatment is most suitable for such patients.Methods
We searched the PubMed, MEDLINE, Embase, and Cochrane Library databases from database inception to August 31, 2020. The quality of the included studies was assessed. We selected the average pain intensity after treatment and the proportion of patients who discontinued treatment because of adverse effects as the outcome indicators for efficacy and safety, respectively. Statistical analyses were performed using Stata, v16.0, and RevMan, v5.3, software.Results
We included eight randomized controlled trials that examined four interventions (pregabalin, gabapentin, carbamazepine, and amitriptyline). Based on the average pain intensity after treatment, the efficacy order from highest to lowest was pregabalin, gabapentin, amitriptyline, carbamazepine, and placebo. Based on the proportion of patients who discontinued treatment because of adverse effects, the order from highest to lowest was pregabalin, amitriptyline, carbamazepine, gabapentin, and placebo. In addition, five studies reported the overall incidence of treatment-related adverse effects for two interventions (pregabalin and gabapentin). According to the pooled analysis of these studies, the order for the overall incidence of treatment-related adverse effects from highest to lowest was pregabalin, gabapentin, and placebo.Conclusions
This study revealed that for patients with SCI-related neuropathic pain, pregabalin was the most effective for relieving pain, whereas gabapentin performed better in aspects associated with drug therapy-related safety.
SUBMITTER: Tong C
PROVIDER: S-EPMC8586377 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI).MethodsPatients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, patient global impression of change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the medical outcomes study-sleep scale and the Hospital anxiety and depression scale.ResultsPregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported.ConclusionsThis study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI.Classification of evidenceThis study provides class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period (p = 0.003, 95% confidence interval = -0.98, -0.20).
| S-EPMC3589291 | biostudies-literature
Project description:BackgroundCharacterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin.MethodsThis was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT)-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and ≥50%). Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale) and the Hospital Anxiety and Depression Scale (HADS) for the pooled studies.ResultsData ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001) and between pain and function on the modified Brief Pain Inventory Interference Index and most individual items (P<0.05).ConclusionGreater functional improvements were generally achieved at higher levels of clinically significant pain reduction. Pregabalin resulted in shifts from placebo toward greater functional improvement with greater pain relief.
| S-EPMC4913987 | biostudies-literature
Project description:BackgroundBased on the molecular expression level, this paper compares lncRNA and mRNA expressions respectively in peripheral blood samples of the patients after SCI with NP and without NP, and screens disease-related biomarkers related to NP after SCI in peripheral blood samples of patients.MethodThe expression spectrum of 25 human peripheral blood samples (12 samples of refractory NP patients after SCI) was downloaded and data were normalized. Screening of GO annotations significantly associated with significant differentially expressed mRNAs and significant involvement of the KEGG pathway. The WGCNA algorithm was used to screen for modules and RNAs that were significantly associated with disease characterization. A co-expression network was constructed to extract the genes involved in the disease pathway from the co-expression network, construct a network of SCI pain-related pathways, and screen important disease-related biomarkers. Quantitative real-time PCR was used to detect the mRNA expression of hub genes.ResultsData were normalized and re-annotated by detection of platform information, resulting in a total of 289 lncRNA and 18197 mRNAs. Screening resulted in 338 significant differentially expressed RNAs that met the threshold requirements. Differentially expressed RNAs were significantly enriched with the brown and magenta modules. Six KEGG signaling pathways were screened in the co-expression network, and three KEGG pathways with direct neuropathic pain were identified. The expression levels of E2F1, MAX, MITF, CTNNA1, and ADORA2B in the disease group were all significantly upregulated (p < 0.01). Compared with the normal group, the expression of OXTR was upregulated.ConclusionWe speculate that there are 7 genes and 2 lncRNAs directly involved in the pain pathway: E2F1, MAX, MITF, CTNNA1, ADORA2B, GRIK3, OXTR, LINC01119, and LINC02447. These molecules may be important for NP after SCI.
| S-EPMC7831171 | biostudies-literature
Project description:Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended. In preclinical SCI models, enhanced reflex withdrawal or pain responses can arise from pathological changes that occur at any point along the sensory neuraxis. Use of quantitative sensory testing for identification of optimal treatment approach may yield improved identification of treatment options and clinical trial design. Additionally, a better understanding of the differences between mechanisms contributing to at- versus below-level neuropathic pain and neuropathic pain versus spasticity may shed insights into novel treatment options. Finally, the role of patient characteristics such as age and sex in pathogenesis of neuropathic SCI pain remains to be addressed.
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Project description:Neuropathic pain represents a primary detrimental outcome of spinal cord injury. A major challenge facing effective management is a lack of surrogate measures to examine the physiology and anatomy of neuropathic pain. To this end, we investigated the relationship between psychophysical responses to tonic heat stimulation and neuropathic pain rating after traumatic spinal cord injury. Subjects provided a continuous rating to 2 min of tonic heat at admission to rehabilitation and again at discharge. Adaptation, temporal summation of pain, and modulation profile (i.e., the relationship between adaptation and temporal summation of pain) were extracted from tonic heat curves for each subject. There was no association between any of the tonic heat outcomes and neuropathic pain severity at admission. The degree of adaptation, the degree of temporal summation of pain, and the modulation profile did not change significantly from admission to discharge. However, changes in modulation profiles between admission and discharge were significantly correlated with changes in neuropathic pain severity (p = 0.027; R 2 = 0.323). The modulation profile may represent an effective measure to track changes in neuropathic pain severity from early to later stages of spinal cord injury.
| S-EPMC6382744 | biostudies-literature
Project description:Neuropathic pain following spinal cord injury involves plastic changes along the whole neuroaxis. Current neuroimaging studies have identified grey matter volume (GMV) and resting-state functional connectivity changes of pain processing regions related to neuropathic pain intensity in spinal cord injury subjects. However, the relationship between the underlying neural processes and pain extent, a complementary characteristic of neuropathic pain, is unknown. We therefore aimed to reveal the neural markers of widespread neuropathic pain in spinal cord injury subjects and hypothesized that those with greater pain extent will show higher GMV and stronger connectivity within pain related regions. Thus, 29 chronic paraplegic subjects and 25 healthy controls underwent clinical and electrophysiological examinations combined with neuroimaging. Paraplegics were demarcated based on neuropathic pain and were thoroughly matched demographically. Our findings indicate that (a) spinal cord injury subjects with neuropathic pain display stronger connectivity between prefrontal cortices and regions involved with sensory integration and multimodal processing, (b) greater neuropathic pain extent, is associated with stronger connectivity between the posterior insular cortex and thalamic sub-regions which partake in the lateral pain system and (c) greater intensity of neuropathic pain is related to stronger connectivity of regions involved with multimodal integration and the affective-motivational component of pain. Overall, this study provides neuroimaging evidence that the pain phenotype of spinal cord injury subjects is related to the underlying function of their resting brain.
| S-EPMC8288099 | biostudies-literature
Project description:Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.
| S-EPMC5405804 | biostudies-literature
Project description:BackgroundThe mechanisms by which mobility function and neuropathic pain are mutually influenced by supraspinal plasticity in motor- and pain-related brain networks following spinal cord injury (SCI) remains poorly understood.ObjectiveTo determine cortical and subcortical resting-state network alterations using power spectral density (PSD) analysis and investigate the relationships between these intrinsic alterations and mobility function and neuropathic pain following SCI.MethodsA total of 41 patients with incomplete SCI and 33 healthy controls were included. The degree of mobility and balance function and severity of neuropathic pain and depressive mood were evaluated. The resting-state functional magnetic resonance imaging data of low-frequency fluctuations were analyzed based on PSD. Differences in PSD values between patients with SCI and controls were assessed using the two-sample t-test (false discovery rate-corrected P < 0.05). The relationship between PSD values and mobility function and pain intensity was assessed using Pearson's correlation coefficient adjusted for the severity of depressive mood.ResultsCompared with healthy controls, lower PSD values in supplementary motor and medial prefrontal areas (the anterior cingulate cortex, ventral medial prefrontal cortex, and superior orbito-prefrontal cortex) were associated with greater pain severity and poorer postural balance and mobility (P < 0.05) in patients with SCI, whereas higher PSD values in the primary motor cortex, premotor cortex, thalamus, and periaqueductal gray were associated with greater pain severity and poorer postural balance and mobility (P < 0.05).ConclusionsCortical and subcortical plastic alterations in intrinsic motor- and pain-related networks were observed in patients with SCI and were simultaneously associated with neuropathic pain intensity and degree of mobility function.
| S-EPMC7453139 | biostudies-literature
Project description:BackgroundMany studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI.MethodsWe performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment.ResultsHere, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM.ConclusionsOur results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI.
| S-EPMC10651991 | biostudies-literature
Project description:BackgroundCentral sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI).MethodsTwo novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP.ResultsEnhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023).ConclusionsThese results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions.SignificanceWe present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.
| S-EPMC9826442 | biostudies-literature