Current evidence for a modulation of low back pain by human genetic variants.
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ABSTRACT:
SUBMITTER: Tegeder I
PROVIDER: S-EPMC6529970 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic low back pain (CLBP) is often without clear underlying pathology. Affective disturbance and dysfunctional pain mechanisms, commonly observed in populations with CLBP, have, therefore, been suggested as potential contributors to CLBP development and maintenance. However, little consensus exists on how these features interact and if they can be targeted using non-invasive brain stimulation. In this pilot trial, 12 participants completed two phases (Active or Sham) of high-definition transcranial direct current stimulation (HD-tDCS) to the medial prefrontal cortex, applied for 20 min on three consecutive days. Clinical pain ratings, questionnaires, and sensitivity to painful cuff pressure were completed at baseline, then 4 trials of conditioned pain modulation (CPM; alone, with distraction using a Flanker task, with positive affect induction, and with negative affect induction using an image slideshow) were performed prior to HD-tDCS on Day 1 and Day 4 (24 h post-HD-tDCS). At baseline, attentional and affective manipulations were effective in inducing the desired state (p < 0.001) but did not significantly change the magnitude of CPM-effect. Active HD-tDCS was unable to significantly alter the magnitude of the shift in valence and arousal due to affective manipulations, nor did it alter the magnitude of CPM under any basal, attentional, or affective manipulation trial significantly on Day 4 compared to sham. The CPM-effect was greater across all manipulations on Day 1 than Day 4 (p < 0.02) but also showed poor reliability across days. Future work is needed to expand upon these findings and better understand how and if HD-tDCS can be used to enhance attentional and affective effects on pain modulation.
| S-EPMC7926794 | biostudies-literature
Project description:Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.
| S-EPMC5041055 | biostudies-literature
Project description:BACKGROUND: Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7-11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise. METHODS: 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7-11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well as haplotype association with change in ODI and VAS LBP, were analyzed using Haploview, linear regression and R-package Haplostats. P-values were not formally corrected for multiple testing as this was an explorative study. RESULTS: Association analysis of individual SNPs adjusted for covariates revealed association of rs4633 and rs4680 with post treatment improvement in VAS LBP (p = 0.02, mean difference (?) = 13.5 and p = 0.02, ? = 14.2 respectively). SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong linkage disequilibrium (LD). A significant association was found with covariates, analgesics (p = 0.001, ? = 18.6); anxiety and depression (p = 0.008, ? = 15.4) and age (p = 0.03, mean difference per year (?) = 0.7) at follow-up. There was a tendency for better improvement among heterozygous patients compared to the homozygous. No association was observed for the analysis of the common haplotypes, these SNPs were situated on. CONCLUSIONS: Results suggest an influence of genetic variants of COMT gene in describing the variation in pain after treatment for low back pain. Replication in large samples with testing for other pain related genes is warranted.
| S-EPMC3453507 | biostudies-literature
Project description:We performed genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic Low Back Pain (LBP) and pain free-controls. T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified.T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (Validation Cohort, n=63) of chronic LBP and healthy controls. Analysis with the Discovery Cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. The majority of these sites were hypo-methylated in women and enriched in genes with functions in the extracellular matrix, the immune system (i.e. cytokines) or in epigenetic processes. In men, we identified a unique chronic LBP DNA methylation signature characterized by significant enrichment for genes from the major histocompatibility complex. A sex-specific polygenic DNA methylation score was generated to evaluate the pain status of each individual and confirmed in The Validation Cohort using pyrosequencing.
2021-11-10 | GSE162350 | GEO
Project description:IntroductionPain-related fear plays a substantial role in chronic low back pain (LBP) by amplifying the experienced disability. Related dysfunctional emotions and cognitions may also affect sensory aspects of pain through a modulatory pathway in which the periaqueductal gray (PAG) and the amygdala play key roles.ObjectivesWe therefore hypothesized a differential amygdala-PAG functional connectivity (FC) in patients with chronic LBP that is modulated by the degree of pain-related fear.MethodsWe used data of a previously reported fMRI study where 20 chronic LBP patients (7 females, mean age = 39.35) and 20 healthy controls (12 females, mean age = 32.10) were asked to observe video clips showing potentially harmful and neutral activities for the back. Pain-related fear was assessed using the Tampa Scale of kinesiophobia (TSK) and Fear Avoidance Beliefs questionnaires (FABQ). Generalized psychophysiological interactions were used to reveal task-based FC.ResultsCompared to controls, patients exhibited a significant decrease in amygdala-PAG-FC (P = 0.022) during observation of harmful activities, but not of neutral activities. Furthermore, amygdala-PAG-FC correlated negatively with Tampa Scale of kinesiophobia scores in patients (R2 = 0.28, P = 0.01) but not with Fear Avoidance Beliefs questionnaires scores.DiscussionOur findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.
| S-EPMC5741307 | biostudies-literature
Project description:BACKGROUND:For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German Disease Management Guideline (NDMG) on nonspecific low back pain is to improve the treatment of patients with this condition. METHODS:The current update of the NDMG on non-specific low back pain is based on articles retrieved by a systematic search of the literature for systematic reviews. Its recommendations for diagnosis and treatment were developed by a collaborative effort of 29 scientific medical societies and organizations and approved in a formal consensus process. RESULTS:If the history and physical examination do not arouse any suspicion of a dangerous underlying cause, no further diagnostic evaluation is indicated for the time being. Passive, reactive measures should be taken only in combination with activating measures, or not at all. When drugs are used for symptomatic treatment, patients should be treated with the most suitable drug in the lowest possible dose and for as short a time as possible. CONCLUSION:A physician should be in charge of the overall care process. The patient should be kept well informed over the entire course of his or her illness and should be encouraged to adopt a healthful lifestyle, including regular physical exercise.
| S-EPMC5769319 | biostudies-other
Project description:PURPOSE:Low back pain (LBP) is a common ailment in most developed countries. Because most cases of LBP are known as 'non-specific', it has been challenging to develop experimental pain models of LBP which reproduce patients' clinical pain. In addition, previous models have limited applicability in a steady-pain-state neuroimaging environment. Thus, this study aims to devise a low back pain model with a simple methodology to induce experimental LBP, which has similar pain properties to patients' clinical pain, and to apply the model in a steady-pain-state neuroimaging study. METHODS:Our low back extension (LBE) pain model was tested on 217 LBP patients outside the magnetic resonance imaging (MRI) scanner to determine the reproducibility of endogenous pain and the similarity to their own clinical pain (STUDY1), and applied in a steady-pain-state functional MRI study (47 LBP patients and 23 healthy controls) to determine its applicability (induced head motions and brain functional connectivity changes; STUDY2). RESULTS:By the LBE pain model, 68.2% of the LBP patients reported increased LBP with high similarity of sensations to their own clinical pain (STUDY1), and the head motions were statistically similar to and correlated with those in resting state (STUDY2). Furthermore, the LBE model altered brain functional connectivity by decreasing the default-mode and the sensorimotor networks, and increasing the salience network, which was significantly associated with the intensity of the induced pain. Conversely, the healthy controls showed increased somatosensory network (but not of the cognitive pain processing). CONCLUSION:Our investigations suggest that our LBE pain model, which increased LBP with high similarity to the LBP patients' own pain sensation and induced patient-specific brain responses with acceptable head motion, could be applied to neuroimaging studies investigating brain responses to different levels of endogenous LBP.
| S-EPMC7263586 | biostudies-literature
Project description: Not available
| S-EPMC8078578 | biostudies-literature
Project description:Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated.In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables.Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients.Clinicaltrials.gov, NCT01179828.
| S-EPMC4574129 | biostudies-other
Project description:BACKGROUND:Although poor standing posture is a known cause of low back pain, the mechanisms involved are unclear. The aim of this study was to clarify the kinetic and posture angle features of standing posture that might influence low back pain. METHODS:Sixty-seven young men were enrolled in this cross-sectional case-control study and were categorized according to whether they did or did not have low back pain. Habitual standing posture was assessed in each group, using a three-dimensional motion analysis system, force plates, and a spinal mouse. Kinetic and posture angle factors were compared between participants with and without low back pain. The relationship between specific features of standing posture and low back pain was analyzed using logistic regression. RESULTS:The intervertebral disc compressive force and the low back moment were significantly greater in the group with low back pain than in the group without low back pain. The intervertebral disc compressive force was the factor most strongly associated with low back pain during static standing. CONCLUSIONS:Logistic regression analysis identified intervertebral disc compressive force as an independent variable associated with low back pain. This finding suggests that increased intervertebral disc compressive force may promote development of low back pain in standing posture.
| S-EPMC6298701 | biostudies-literature