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We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls.
Learn More >Although many national surveys have been published on migraine epidemiology, such as that carried out by Wolfson et al in Canada [1], recent information on global epidemiologic burden of this condition has not been published. Therefore, in this succinct report we present an update on worldwide epidemiology of migraine, based on data retrieved from the official database of the World Health Organization (WHO) [2].
Learn More >We previously reported that early life stress (ELS) dysregulated glucocorticoid receptor (GR) and corticotrophin-releasing hormone (CRH) expression in the central nucleus of the amygdala (CeA). Epigenetic modifications serve as memories of adverse events that occurred during early life. Therefore, we hypothesized that epigenetic mechanisms alter GR and CRH expression in the CeA and underlie chronic visceral pain after ELS.
Learn More >Altered pronociceptive and antinociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions, alterations are well-established, but in populations with low back pain (LBP), there remains considerable debate whether these mechanisms are altered. The present systematic review aimed to address this issue by identifying studies assessing conditioned pain modulation (CPM) and/or temporal summation of pain (TSP) in patients with LBP, comparing with either a healthy control group or using a method with reference data available. Qualitative synthesis and quantitative meta-analysis of group differences were performed. For CPM and TSP, 20 and 29 original articles were eligible, with data for meta-analysis obtainable from 18 (1500 patients and 505 controls) and 27 (1507 patients and 1127 controls) studies, respectively. Most studies were of poor-to-fair quality with significant heterogeneity in study size, population, assessment methodology, and outcome. Nonetheless, CPM was impaired in patients with LBP compared with controls (standardized mean difference = -0.44 [-0.64 to -0.23], P < 0.001), and the magnitude of this impairment was related to pain chronicity (acute/recurrent vs chronic, P = 0.003), duration (RS = -0.62, P = 0.006), and severity (RS = -0.54, P = 0.02). Temporal summation of pain was facilitated in patients with LBP compared with controls (standardized mean difference = 0.50 [0.29-0.72], P < 0.001), and the magnitude of this facilitation was weakly related to pain severity (RS= 0.41, P = 0.04) and appeared to be influenced by test modality (P < 0.001). Impaired CPM and facilitated TSP were present in patients with LBP compared with controls, although the magnitude of differences was small which may direct future research on the clinical utility.
Learn More >Allodynia is a common feature of neuropathic pain with few validated clinical evaluation options. We identified a need to estimate the measurement properties of the standardised evaluation procedure for static mechanical allodynia severity popularised by the somatosensory rehabilitation of pain method, known as the rainbow pain scale. This study (www.clinicaltrials.gov. NCT02070367) undertook preliminary investigation of the inter-rater and test-retest reliability of the rainbow pain scale. Persons with pain in one upper extremity after Complex Regional Pain Syndrome, a peripheral nerve injury or a recent hand fracture were recruited for assessment of static mechanical allodynia threshold using calibrated monofilaments by two raters at baseline, and repeated assessment one week later. Single measures estimates suggested inter-rater reliability was substantial for the rainbow pain scale [intra-class correlation coefficient = 0.78 ( = 31), < 0.001]. Test-retest reliability was also excellent at with an intraclass correlation coefficient of 0.87 [ = 28, < 0.001]. However, confidence intervals suggest the true values could be more moderate, with lower bounds of the 95% confidence interval at 0.60 and 0.74, respectively. This pilot study has generated preliminary support for the inter-rater and test-retest reliability of the rainbow pain scale. Future studies should seek to increase confidence in estimates of reliability, and estimate validity and responsiveness to change in persons with somatosensory disorders.
Learn More >In the absence of cure, the main objectives in the management of patients with mitochondrial disease are symptom control and prevention of complications. While pain is a complicating symptom in many chronic diseases and is known to have a clear impact on quality of life, its prevalence and severity in people with mitochondrial disease is unknown. We conducted a survey of pain symptoms in patients with genetically confirmed mitochondrial disease from two UK mitochondrial disease specialist centres. The majority (66.7%) of patients had chronic pain which was primarily of neuropathic nature. Presence of pain did not significantly impact overall quality of life. The m.3243A>G MTTL1 mutation was associated with higher pain severity and increased the likelihood of neuropathic pain compared to other causative nuclear and mitochondrial gene mutations. Although previously not considered a core symptom in people with mitochondrial disease, pain is a common clinical manifestation, frequently of neuropathic nature, and influenced by genotype. Therefore, pain-related symptoms should be carefully characterised and actively managed in this patient population.
Learn More >Opioid-based analgesia is the most common method for pain control in the postoperative period. Limited data exist to compare the adequacy of pain control in the post thyroidectomy period with nonopioid-based analgesia. We aimed to evaluate the efficacy of nonopioid-based, postoperative analgesia.
Learn More >Observational epidemiological studies indicate that endometriosis and migraine co-occur within individuals more than expected by chance. However, the aetiology and biological mechanisms underlying their comorbidity remain unknown. Here we examined the relationship between endometriosis and migraine using genome-wide association study (GWAS) data. Single nucleotide polymorphism (SNP) effect concordance analysis found a significant concordance of SNP risk effects across endometriosis and migraine GWAS. Linkage disequilibrium score regression analysis found a positive and highly significant genetic correlation ( = 0.38, = 2.30 × 10) between endometriosis and migraine. A meta-analysis of endometriosis and migraine GWAS data did not reveal novel genome-wide significant SNPs, and Mendelian randomisation analysis found no evidence for a causal relationship between the two traits. However, gene-based analyses identified two novel loci for migraine. Also, we found significant enrichment of genes nominally associated ( < 0.05) with both traits ( = 9.83 × 10). Combining gene-based p-values across endometriosis and migraine, three genes, two ( of which are at novel loci, were genome-wide significant. Genes having < 0.1 for both endometriosis and migraine ( = 1.85 ×10°) were significantly enriched for biological pathways, including interleukin-1 receptor binding, focal adhesion-PI3K-Akt-mTOR-signaling, MAPK and TNF-α signalling. Our findings further confirm the comorbidity of endometriosis and migraine and indicate a non-causal relationship between the two traits, with shared genetically-controlled biological mechanisms underlying the co-occurrence of the two disorders.
Learn More >For over two decades, purinergic signaling in microglia has persisted in the spotlight as a major pathomechanism of chronic pain. Of the many purinoreceptors, the P2X4R of the ionotropic family has a well-described causal role underlying chronic neuropathic pain. This review will first briefly examine microglial P2X4R signaling in the spinal cord as it relates to chronic pain through a historical lens, followed by a more in-depth examination of recent work, which has revealed major sex differences. We also discuss the generalizability of sex differences in microglial and P2X4R signaling in other pain conditions, as well as in non-spinal regions. Finally, we speculate on remaining gaps in the literature as well as what can be done to address them with the ultimate goal of using our collective knowledge to treat chronic pain effectively and in both sexes. SIGNIFICANCE STATEMENT: Effective treatments are lacking for chronic pain sufferers, and this may be explained by the vast sex differences underlying chronic pain mechanisms. In this Minireview, we focus on the roles of microglia and P2X4R in chronic pain, with specific attention to the circumstances under which these pathomechanisms differ between males and females. By delineating the ways in which pain occurs differently between the sexes, we can start developing successful therapies for all.
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