The association between genome-wide polymorphisms and chronic postoperative pain: a prospective observational study.
ABSTRACT: Chronic postoperative pain is common and can have a negative impact on quality of life. Recent studies show that genetic risk factors are likely to play a role, although only gene-targeted analysis has been used to date. This is the first genome-wide association study to identify single-nucleotide polymorphisms associated with the development of chronic postoperative pain based on two independent cohorts. In a discovery cohort, 330 women scheduled for hysterectomy were genotyped. A case-control association analysis compared patients without chronic postoperative pain and the 34 who had severe chronic postoperative pain 3 months after surgery. No single-nucleotide polymorphisms reached genome-wide significance, but several showed suggestive associations with chronic postoperative pain (p < 1 × 10-5 ). Single-nucleotide polymorphisms with significance p < 1 × 10-5 were followed up in a replication cohort consisting of 203 men and women scheduled for orthopaedic or abdominal surgery. Ten of these patients developed severe chronic postoperative pain. A single-nucleotide polymorphism in NAV3 was significantly replicated with chronic postoperative pain in the replication cohort (p = 0.009). Meta-analysis revealed that two loci (IQGAP1 and CRTC3) were significantly associated with chronic postoperative pain at 3 months (IQGAP1 p = 3.93 × 10-6 ? = 2.3863, CRTC3 p = 2.26 × 10-6 , ? = 2.4209). The present genome-wide association study provides initial evidence for genetic risk factors of chronic postoperative pain and supports follow-up studies.
Project description:Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown.Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele.Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.
Project description:Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort.Intensity of cold (+2-4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression.There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found.SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied.
Project description:OBJECTIVE:Postoperative chronic pain is characterized by high incidence, long duration, and complex pathogenesis. The purpose of this study was to investigate the correlation between the single nucleotide polymorphisms of the CCL2 gene rs4586 (g.5974T>C), CALCA rs3781719 (-692T>C), CX3CL1 rs614230 (2342C>T), and the risk of postoperative chronic pain in Chinese Han women. METHODS:We analyzed the CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 single nucleotide polymorphism (SNPs) of 350 Chinese Han women with chronic postsurgical pain (CPSP) 6 months after cesarean section and 350 healthy women without chronic pain (HC). The levels of CCL2, CALCA, and CX3CL1 in serum were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:The CCL2 rs4586 T allele and the CX3CL1 gene rs614230C allele were protective factors for CPSP risk (adjusted OR?=?0.766, 95% CI: 0.675-0.865 and OR?=?0.336, 95% CI: 0.644-0.835). The CALCA gene rs3781719C allele was a risk factor for CPSP (adjusted OR?=?1.273, 95% CI: 1.125-1.424). CCL2 rs4586, CX3CL1 gene rs614230, and CALCA gene rs3781719 locus gene polymorphisms were associated with serum CCL2, CX3CL1, and CALCA protein levels. CONCLUSION:Our results support that CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 gene polymorphism are associated with the occurrence of chronic pain after cesarean section in Chinese Han women.
Project description:Objective:To explore the effect of genetic polymorphisms of cytokines on the dosage of sufentanil for patient-controlled intravenous analgesia (PCIA) after radical lung cancer surgery. Methods:A total of 100 patients, aged 18 years and above, with ASA grade ?-? and body mass index (BMI) 18.5 to 30, and who were scheduled for radical lung cancer surgery under total intravenous anaesthesia with PCIA of sufentanil from September 2015 to March 2016, were selected. DNA was collected from peripheral blood samples before surgery, and the iMLDRTM multiple single-nucleotide polymorphism typing kit was used to detect 16 related single-nucleotide polymorphism (SNP) sites of interleukin-1A (IL-1A), interleukin-1? (IL-1?), interleukin-1RN (IL-1RN), interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), interleukin-10 (IL-10), tumour necrosis factor (TNF), nuclear factor kappa-B1 (NF?B1), REL (REL proto-oncogene, NF-kB subunit), and nuclear factor kappa-B inhibitor alpha (NF?BIA). The general characteristics of patients, surgery and anaesthesia data, postoperative resting VAS pain scores, postoperative opioid dosages of sufentanil for PCIA and opioid-related adverse events were recorded. The effects of the examined genetic polymorphisms of the cytokines on the dosage of sufentanil were analysed. Results:Eight of 100 patients withdrew for various reasons, and, eventually, 92 patients were included. The patients' resting visual analogue scale (VAS) scores at 24 h, 48 h, and 72 h after surgery were 2.3 ± 1.2, 2.0 ± 0.9, and 1.9 ± 1.0, respectively. The total amounts of sufentanil used were 34.7 ± 10.5 ?g, 65.2 ± 13.7 ?g, and 94.7 ± 11.6 ?g, respectively. We found that the TT genotype of NF?BIA rs696 had higher PCIA sufentanil dosages than the CC genotype and the CT genotype at 48-72 h postoperation (p=0.023, p=0.025, respectively). Conclusion:The genetic polymorphisms of the cytokine NF?BIA rs696 might affect the dosage of sufentanil for PCIA after radical lung cancer surgery. The specific mechanism needs further study.
Project description:Pediatric tonsillectomy involves an often painful and lengthy recovery period, yet the extended recovery process is largely unknown. This article describes postoperative recovery outcomes for 121 children aged 4 to 15 (mean 6.6 years, SD = 2.3) years enrolled in 1 of 2 clinical trials of analgesia safety and efficacy after tonsillectomy. Postoperative analgesia included scheduled opioid analgesic plus acetaminophen/ibuprofen medication use (first 5 days) and "as-needed" use (last 5 days). Clinical recovery as measured daily by the Parents' Postoperative Pain Measure (PPPM; an observational/behavioral pain measure), children's self-reported pain scores, side-effect assessments, need for unanticipated medical care, and satisfaction with recovery over 10 days was assessed. Higher Parents' Postoperative Pain Measure scores were correlated with poorer sleep, receipt of breakthrough analgesics, distressing side effects, higher self-reported pain scores, and need for unanticipated medical care. Higher self-reported pain scores were associated with more distressing adverse events, including nausea, vomiting, insomnia, lower parent satisfaction, and unplanned medical visits and hospitalizations. Pain and symptoms improved over time, although 24% of the children were still experiencing clinically significant pain on day 10. Scheduled, multimodal analgesia and discharge education that sets realistic expectations is important. This study adds to the emerging body of literature that some children experience significant postoperative pain for an extended period after tonsillectomy.
Project description:P2X7 is a nonselective cation channel activated by extracellular ATP. P2X7 activation contributes to the proinflammatory response to injury or bacterial invasion and mediates apoptosis. Recently, P2X7 function has been linked to chronic inflammatory and neuropathic pain. P2X7 may contribute to pain modulation both by effects on peripheral tissue injury underlying clinical pain states, and through alterations in central nervous system processing, as suggested by animal models. To further test its role in pain sensitivity, we examined whether variation within the P2RX7 gene, which encodes the P2X7 receptor, was associated with experimentally induced pain in human patients. Experimental pain was assessed in Tromsø 6, a longitudinal and cross-sectional population-based study (N = 3016), and the BrePainGen cohort, consisting of patients who underwent breast cancer surgery (N = 831). For both cohorts, experimental pain intensity and tolerance were assessed with the cold-pressor test. In addition, multisite chronic pain was assessed in Tromsø 6 and pain intensity 1 week after surgery was assessed in BrePainGen. We tested whether the single-nucleotide polymorphism rs7958311, previously implicated in clinical pain, was associated with experimental and clinical pain phenotypes. In addition, we examined effects of single-nucleotide polymorphisms rs208294 and rs208296, for which previous results have been equivocal. Rs7958311 was associated with experimental pain intensity in the meta-analysis of both cohorts. Significant associations were also found for multisite pain and postoperative pain. Our results strengthen the existing evidence and suggest that P2X7 and genetic variation in the P2RX7-gene may be involved in the modulation of human pain sensitivity.
Project description:The aim of the present study was to compare clinically the incidence of postoperative pain after endodontic treatment using the Reciproc System, taking into account the operator's experience.One hundred patients scheduled for routine endodontic treatment were enrolled in this study. Endodontic treatment was carried out in a single visit by undergraduate and postgraduate students. The chemomechanical preparation of root canals was performed with Reciproc instruments. Pretreatment and postoperative pain was recorded using a visual analogue scale (VAS). Postoperative pain and the need for analgesic consumption were assessed at 4, 8, 16, 24, 48 and 72 hours post-treatment. The data were analyzed using the Mann-Whitney U and Chi-Square test, and the significance was set at P<0.05.The mean value of pain after root canal treatment was 1.13±1.94 and 1.91±2.07 on a VAS between 0 and 10 in treatments performed by undergraduate and postgraduate students, respectively. There was a significant difference in the incidence of postoperative pain between the two groups (P<0.05).The prevalence of postoperative pain was high in the treatments performed by postgraduate students in comparison with undergraduate students. This suggests that operator experience has an influence on the prevalence of postoperative pain after root canal treatment. Key words:Post-endodontic pain, root canal treatment, reciprocating systems, Expert operators Inexperienced operators.
Project description:The use of laparoscopic surgeries is escalating thanks to their advantages over the open surgeries. However, several complications can be observed following laparoscopy operation. Postoperative pain is a major concern in cholecystectomy surgeries. Pain can be both experienced in operated areas and radiated to the right shoulder. Acetazolamide is used for glaucoma, acute mountain sickness prophylaxis, and epilepsy in few patients with recurrent epilepsy. It seems that patients' pain can be reduced by preventing carbonic acid production in abdomen after operation.We aimed at evaluating if administration of acetazolamide preoperatively could affect early or late postoperative pain following laparoscopic surgery.In a randomized-controlled clinical trial study, 70 subjects (30 - 60 years) scheduled for laparoscopic cholecystectomy were included after obtaining a written informed consent. Patients were divided into two groups randomly (intervention and control). The intervention group received 5 mg/kg oral acetazolamide one hour before the operation. The control group did not receive any further medication.Administration of a single dose of acetazolamide did not have any statistically significant impact on sleep quality (P = 1.000). Moreover, there was no statistically significant difference between groups regarding nausea and vomiting on single dose administration of acetazolamide (P = 1.000). Single dose of acetazolamide was associated with statistically significant decrease in shoulder pain immediately after laparoscopy (P = 0.017). However, there was no statistically significant difference regarding shoulder pain between the studied groups 2, 4, 6, 8, 10, 12, and 24 hours after laparoscopy. Single dose of acetazolamide did not significantly affect analgesic administration in 2, 4, 6, 8, 10, 12, and 24 hours after laparoscopy.Single dose of acetazolamide was associated with statistically significant decrease in shoulder pain immediately after laparoscopy. However, this effect was limited to the first postoperative hours and it failed to reduce postoperative pain of right shoulder during 24 hours after the operation.
Project description:To examine the prognostic value of the Fear Avoidance Model (FAM) variables when predicting pain intensity and disability 10-weeks postoperative following lumbar disc surgery.We recruited patients scheduled for first-time, single level lumbar disc surgery. The following aspects of the FAM were assessed at preoperative baseline and after 10 postoperative weeks: numeric pain rating scale (0-10) for leg and back pain intensity separately, Pain Catastrophizing Scale (PCS), Fear Avoidance Beliefs Questionnaire (FABQ), Beck Depression Inventory (BDI), Oswestry Disability Questionnaire (ODI), and the International Physical Activity Questionnaire (IPAQ). Multivariate regression models were used to examine the best combination of baseline FAM variables to predict the 10-week leg pain, back pain, and disability. All multivariate models were adjusted for age and sex.60 patients (30 females, mean [SD] age = 40.4 [9.5]) were enrolled. All FAM measures correlated with disability at baseline. Adding FAM variables to each of the stepwise multiple linear regression model explained a significant amount of the variance in disability (Adj. R2 = .38, p < .001), leg pain intensity (Adj. R2 = .25, p = .001), and back pain intensity Adj. R2 = .32, p < .001 at 10-weeks). After adjusting for age and gender, BDI and FABQ-work subscale were the only significant predictors added to each of the prediction models for the 10-week clinical outcome (leg pain, back pain, and ODI).BDI and FABQ-work subscale variables are associated with baseline pain intensity and disability and predict short-term pain and disability following lumbar disc surgery. Measuring these variables in patients being considered for lumbar disc surgery may improve patient outcome.
Project description:OBJECTIVE: The present study aims to observe the influence of single-nucleotide polymorphisms (SNPs) in the ADRB1 gene on individual differences in pain sensitivity. METHODS: We analyzed the associations between pain sensitivity and ADRB1 gene SNPs (A145 G and G1165 C) in 324 Chinese patients who underwent surgery. The genotyping was performed using PCR-RFLP technique. RESULTS: The patients who carried the A-allele of the A145 G SNP were more sensitive to cold pressor-induced pain than those who did not carry this allele (P < 0.05). We did not found G1165 C polymorphism associated with pain sensitive in the present study. The haplotype analysis revealed A-C haplotype carriers have reduced fentanyl use in 24-h postoperative (P < 0.05). CONCLUSION: ADRB1 gene polymorphisms are associated with pain and analgesic sensitivity.