Pain
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Dysmenorrhea is a common chronic pelvic pain syndrome affecting women of childbearing potential. Family studies suggest that genetic background influences the severity of dysmenorrhea, but genetic predisposition and molecular mechanisms underlying dysmenorrhea are not understood. In this study, we conduct the first genome-wide association study to identify genetic factors associated with dysmenorrhea pain severity. ⋯ Participants reporting extreme dysmenorrhea pain were more likely to report being positive for endometriosis, polycystic ovarian syndrome, depression, and other psychiatric disorders. Our results indicate that dysmenorrhea pain severity is partly genetically determined. NGF already has an established role in chronic pain disorders, and our findings suggest that NGF may be an important mediator for gynaecological/pelvic pain in the viscera.
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Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously. ⋯ In the Indian cohort, 14.5% of the variance in morphine use score was explained by IL1B rs1143634 (increased) and TGFB1 rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variant COMT rs4680 genotypes (P = 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.
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Fibromyalgia syndrome (FMS) is a chronic widespread pain condition probably comprising subgroups with different underlying pathomechanisms. There is increasing evidence for small nerve fiber impairment in subgroups of patients with FMS. MicroRNAs (miRNAs) regulate molecular factors determining nerve de- and re-generation. ⋯ We found 51 aberrantly expressed miRNAs in white blood cells of patients with FMS, of which miR-let-7d correlated with reduced small nerve fiber density in patients with FMS. Furthermore, we demonstrated miR-let-7d and its downstream target insulin-like growth factor-1 receptor as being aberrantly expressed in skin of patients with FMS with small nerve fiber impairment. Our study gives further evidence of small nerve fiber pathology in FMS subgroups and provides a missing link in the pathomechanism that may lead to small fiber loss in subgroups of patients with FMS.
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The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver. In this study, the influence of OCT1 genetic polymorphisms on pharmacokinetics and analgesic efficacy of tramadol in patients recovering from surgery was analyzed in addition to the CYP2D6 genotype. Postoperative patients who received tramadol through patient-controlled analgesia were enrolled. ⋯ Plasma areas under the concentration-time curves of (+)O-desmethyltramadol were 111.8 (95% confidence interval: 63.4-160.1), 80.2 (65.1-95.3), and 64.5 (51.9-77.2) h·ng·mL in carriers of 0, 1, or 2 active OCT1 alleles (P = 0.03). Loss of OCT1 function resulted in reduced tramadol consumption and increased plasma concentrations of (+)O-desmethyltramadol in patients recovering from surgery. Therefore, analyzing OCT1 next to CYP2D6 genotype might further improve future genotype-dependent dose recommendations for tramadol.
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Studies have suggested that alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40 to 69 years, registered at medical practices nationwide. ⋯ In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (nondrinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% confidence intervals [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females, there was a decrease in the proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (nondrinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption because of health concerns, after adjustment for potential confounding factors.