Genetic predictors of human chronic pain conditions.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

https://depts.washington.edu/anesth/care/pain/forms/IMMPACT%20Recommendations.pdf

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Novel diagnostic and prognostic methods for disc degeneration and low back pain

Human Genetic Variability Contributes to Postoperative Morphine Consumption

Background Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. Methods A systematic review of the literature was performed, and additional literature was obtained by reference tracking. The primary outcome was CPSP, defined as pain at least 2 months after the surgery. Studies performed exclusively in animals were excluded. Results Out of the 1001 identified studies, 14 studies were selected for inclusion. These studies described 5269 participants in 17 cohorts. A meta-analysis was not possible because of heterogeneity of data and data analysis. Associations with the prevalence or severity of CPSP were reported for genetic variants in the COMT gene, OPRM1, potassium channel genes, GCH1, CACNG, CHRNA6, P2X7R, cytokine-associated genes, human leucocyte antigens, DRD2, and ATXN1. Conclusions Research on the topic of genetic variants associated with CPSP is still in its initial phase. Hypothesis-free, genome-wide association studies on large cohorts are needed in this field. In addition, future studies may also integrate genetic risk factors and patient characteristic, clinical, and psychological predictors for CPSP.

Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review.

Background
This study was aimed at the evaluation of the relationship between genetic polymorphisms of catechol-O-methyltransferase (COMT) (rs4680:A > G—Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C > G) and pain sensitivity after lumbar discectomy.

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Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases

Objective Lumbar intervertebral disk herniation (LDH) is considered one of the major risk factors for lower back pain, mainly caused by irritation of a spinal nerve or its root. One of the genes related to pain perception is SCN9A, which encodes the voltage gated sodium channel NaV1.7, a key molecule involved in peripheral pain processing. It had been presented before that a common polymorphism within SCN9A (rs6746030: G > A, R1150W) might influence nociception in the general population. Hence, the present study was aimed at investigating the association between SCN9A polymorphism and pain sensitivity. Methods Pain intensity was measured by means of the visual analog pain scale (VAS) in 176 Caucasian patients with a history of leg and back pain who had been diagnosed with LDH and underwent lumbar discectomy. SCN9A polymorphism was determined by means of TaqMan assay. Results A significantly higher preoperative back pain intensity was observed among rs6746030 A minor allele carriers, compared with GG homozygotes (VAS = 7.5 ± 2.4 vs 6.5 ± 2.7, P = 0.012). Similarly, A allele carriers were characterized by higher values of leg pain prior to surgery (VAS = 7.8 ± 2.3 vs 6.8 ± 2.6, P = 0.013). However, postoperative improvement in pain reduction was similar in both groups. Conclusions Our results suggest that the SCN9A rs6746030 polymorphism may be associated with pain intensity in patients suffering from symptomatic disc herniation.

/pdf/common-missense-variant-of-scn9a-gene-is-associated-with-4nfjmwhxwx.pdf

Common Missense Variant of SCN9A Gene Is Associated with Pain Intensity in Patients with Chronic Pain from Disc Herniation

Background and purpose An analysis of predictors of mortality in patients with ruptured intracranial aneurysm is an important aspect in the assessment of outcome. The aim of the study was to analyse factors determining mortality risk after the surgical treatment of ruptured internal carotid artery (ICA) aneurysm. Material and methods This study comprised 242 patients operated on between 1997 and 2006 in the Neurosurgery Department of the Medical University Hospital in Gdansk, Poland. Multivariate logistic regression, ROC curves (for model assessment as a mortality classifier) and population attributable risk for contribution of individual factor mortality explanation were used to assess factors related to in-hospital mortality. Results 14.9% of patients died postoperatively. In univariate analysis, increased risk of death was related to the Glasgow Coma Scale score, WFNS score, Hunt-Hess and Fisher grade, preoperative neurological deficit, delayed cerebral ischaemia (DCI), trapping and bypass operative method. Multivariate analysis revealed two independent predictors of in-hospital mortality: DCI and Hunt-Hess grade. 91% of mortality risk was attributed to grade 4 or 5 in Hunt-Hess scale and DCI. The dominant predictor of survival was the Hunt-Hess scale. Increase by one grade in the Hunt-Hess scale resulted in two-fold increase of in-hospital mortality risk. Conclusions Postoperative mortality after ICA aneurysm rupture is determined by clinical status at admission and the occurrence of DCI.

Predictors of postoperative mortality in ruptured aneurysms of internal carotid artery.

Background and purpose: An analysis of predictors of mor tality in patients with ruptured intracranial aneurysm is an im portant aspect in the assessment of outcome. The aim of the study was to analyse factors determining mortality risk after the surgical treatment of ruptured internal carotid artery (ICA) aneurysm. Material and methods: This study comprised 242 patients operated on between 1997 and 2006 in the Neurosurgery De partment of the Medical University Hospital in Gdansk, Poland. Multivariate logistic regression, ROC curves (for model assess ment as a mortality classifier) and population attributable risk for contribution of individual factor mortality explanation were used to assess factors related to in-hospital mortality. Results: 14.9% of patients died postoperatively. In univariate analysis, increased risk of death was related to the Glasgow Coma Scale score, WFNS score, Hunt-Hess and Fisher grade, preoperative neurological deficit, delayed cerebral ischaemia (DCI), trapping and bypass operative method. Multivariate analysis revealed two independent predictors of in-hospital mortality: DCI and Hunt-Hess grade. 91% of mortality risk was attributed to grade 4 or 5 in Hunt-Hess scale and DCI. The dominant predictor of survival was the Hunt-Hess scale. Increase by one grade in the Hunt-Hess scale resulted in twofold increase of in-hospital mortality risk. Conclusions: Postoperative mortality after ICA aneurysm rup ture is determined by clinical status at admission and the oc currence of DCI.

Predictors of postoperative mortality in ruptured aneurysms of internal carotid artery Czynniki rokownicze œmiertelnoœci po operacji pêkniêtych têtniaków têtnicy szyjnej wewnêtrznej

Marcin Rut

Papers

Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases

Common Missense Variant of SCN9A Gene Is Associated with Pain Intensity in Patients with Chronic Pain from Disc Herniation

Predictors of postoperative mortality in ruptured aneurysms of internal carotid artery.

Predictors of postoperative mortality in ruptured aneurysms of internal carotid artery Czynniki rokownicze œmiertelnoœci po operacji pêkniêtych têtniaków têtnicy szyjnej wewnêtrznej