Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-analyses.

BACKGROUND: Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation. METHODS: This article is a systematic review of genetic variants associated with postsurgical pain in humans, assessing association with postsurgical pain scores and opioid use in both acute (0 to 48 h postoperatively) and chronic (at least 3 months postoperatively) settings. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from 2000 to 2022 for studies using search terms related to genetic variants and postsurgical pain in humans. English-language studies in adult patients examining associations of one or more genetic variants with postsurgical pain were included. The primary outcome was association of genetic variants with either acute or chronic postsurgical pain. Pain was measured by patient-reported pain score or analgesic or opioid consumption. RESULTS: A total of 163 studies were included, evaluating 129 unique genes and 594 unique genetic variants. Many of the reported significant associations fail to be replicated in other studies. Meta-analyses were performed for seven variants for which there was sufficient data (OPRM1 rs1799971; COMT rs4680, rs4818, rs4633, and rs6269; and ABCB1 rs1045642 and rs2032582). Only two variants were associated with small differences in postsurgical pain: OPRM1 rs1799971 (for acute postsurgical opioid use standard mean difference = 0.25; 95% CI, 0.16 to 0.35; cohort size, 8,227; acute postsurgical pain score standard mean difference = 0.20; 95% CI, 0.09 to 0.31; cohort size, 4,619) and COMT rs4680 (chronic postsurgical pain score standard mean difference = 0.26; 95% CI, 0.08 to 0.44; cohort size, 1,726). CONCLUSIONS: Despite much published data, only two alleles have a small association with postsurgical pain. Small sample sizes, potential confounding variables, and inconsistent findings underscore the need to examine larger cohorts with consistent outcome measures.

What motivates dentists to work in prisons? A qualitative exploration.

OBJECTIVE: To explore what motivates dentists to work in prisons using Vroom's theoretical model of motivation as an explanatory framework. METHOD: In-depth interviews were conducted with ten of the 15 dentists working in Scottish prisons. The focus was to explore their motivations to work in Scottish prisons. The data were analysed using a thematic framework based on the three motivational dimensions of expectancy, instrumentality and valence. RESULTS: The dentists had the skills to help improve their prisoner-patients' oral health but their efforts were often hindered by institutional rationing and the requirement to fit in with prison routines and procedures (expectancy). Despite these institutional difficulties the dentists experienced work rewards associated with the improvement in the prisoners' oral health (instrumentality). Finally, the dentists experienced a feeling of personal worth and a sense of commitment to providing care to Scottish prisoners (valence). CONCLUSIONS: The dentists' motivation to work in Scottish prisons may be explained by Vroom's Expectancy Theory. The dentists' motivation is characterised by their beliefs that their work will improve clinical outcomes which will be rewarded by the satisfaction experienced when they overcome environmental obstacles and provide oral health care for their prisoner-patients.

Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.

Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. We then compared our study (Charing Cross Hospital prospective collection) with that of an independent prefrontal cortex dataset from the Harvard Brain Bank. We report the first direct comparison between two independent studies. A total of 51 gene expression changes have been identified that are common between the schizophrenia cohorts, and 49 show the same direction of disease-associated regulation. In particular, changes were observed in gene sets associated with synaptic vesicle recycling, transmitter release and cytoskeletal dynamics. This strongly suggests multiple, small but synergistic changes in gene expression that affect nerve terminal function.