Pain
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Randomized Controlled Trial
GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.
Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. ⋯ Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.
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Persistent pain after breast cancer surgery is a common clinical problem. Given the role of potassium channels in modulating neuronal excitability, coupled with recently published genetic associations with preoperative breast pain, we hypothesized that variations in potassium channel genes will be associated with persistent postsurgical breast pain. In this study, associations between 10 potassium channel genes and persistent breast pain were evaluated. ⋯ In addition, 3 SNPs and 1 haplotype across 4 genes (ie, KCND2, KCNJ3, KCNJ6, KCNK9) were associated with membership in the Severe Pain class. These findings suggest that variations in potassium channel genes are associated with both mild and severe persistent breast pain after breast cancer surgery. Although findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.
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Although the co-occurrence of low back pain (LBP) and depression is common, the nature of this association remains unclear. We aimed to investigate whether symptoms of depression are associated with LBP after adjusting for various confounders, including genetics. We used cross-sectional data from 2148 twins from the Murcia Twin Registry, Spain. ⋯ Symptoms of depression and anxiety were associated with higher prevalence of LBP in the total sample analysis (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.31-2.05), and this relationship was stronger in the subsequent case-control analysis (OR, 1.74; 95% CI, 1.13-2.69) and dizygotic case-control analysis (OR, 2.39; 95% CI, 1.39-4.08) but disappeared when the analysis was conducted for monozygotic twins (OR, 0.92; 95% CI, 0.42-2.05). A similar pattern was found for state and trait depression. The depression-LBP relationship disappears when high levels of control for confounding factors are applied and seems to be driven by genetic or environmental factors that influence both conditions.
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Randomized Controlled Trial
A new objective method for acquisition and quantification of reflex receptive fields.
The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex correlated with pain perception. Assessment of this objective physiological measure constitutes the core of existing methods for quantification of reflex receptive fields (RRFs), which however still suffer from a certain degree of subjective involvement. This article proposes a strictly objective methodology for RRF quantification based on automated identification of NWR thresholds (NWR-Ts). ⋯ The NWR-T-based quantifications required a smaller sample size than any of the existing RRF measures to detect a clinically relevant effect in a crossover study design involving more than 1 session. Of all measures, quantification from mapping of inversed NWR-Ts demonstrated superior reliability both within (CR, 0.25) and between sessions (CR, 0.28). The study presents a more reliable and robust quantification of the RRF to be used as biomarker of pain hypersensitivity in clinical and experimental research.