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Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.

ABSTRACT: Previous research has identified many genetic polymorphisms that appear to mediate the effects of opioid drugs. However, the relationship between genetic polymorphisms and the severity of opioid withdrawal has not yet been characterized.Data were collected from 48 daily heroin users who previously completed a standardized abstinence-induced or naloxone-precipitated withdrawal procedure to assess opioid dependence. The total withdrawal severity score (based on the COWS) from this procedure was correlated with genotype information for variants of OPRM1 (rs1799971; rs6848893), OPRD1 (rs10753331; rs2234918; rs581111; rs678849; rs1042114), and OPRK1 (rs6473797; rs963549). Genotype and other participant variables (age, race, sex, duration of drug use, concomitant drug use, route of opioid use) were used as predictors.Of these variables, those individually correlated with a p?

SUBMITTER: Jones JD

PROVIDER: S-EPMC5444323 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.

Jones Jermaine D JD Luba Rachel R RR Vogelman Jonathan L JL Comer Sandra D SD

The American journal on addictions 20151221 1

<h4>Background</h4>Previous research has identified many genetic polymorphisms that appear to mediate the effects of opioid drugs. However, the relationship between genetic polymorphisms and the severity of opioid withdrawal has not yet been characterized.<h4>Methods</h4>Data were collected from 48 daily heroin users who previously completed a standardized abstinence-induced or naloxone-precipitated withdrawal procedure to assess opioid dependence. The total withdrawal severity score (based on t ...[more]

PMID: 26692286

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Project description:Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30 mg, subcutaneous, four-times daily) underwent a naloxone (0.4 mg, IM = intramuscular) challenge session to precipitate withdrawal. Area-under-the-curve (AUC) values from self-reported withdrawal ratings during the challenge session were analyzed using K-means clustering, revealing two phenotype groups. Withdrawal and retention from the subsequent 14-day double-blind, double-dummy RCT comparing three study medications (clonidine, tramadol-ER, and buprenorphine) were evaluated as a function of phenotype. Cluster analyses suggested HIGH (N = 37; mean [SD] subjective opiate withdrawal scale [SOWS]-AUC 123.7 [65.8]) and LOW (N = 52; SOWS-AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were significantly more female and had lower body mass indices than LOW participants; no drug-use variables were significant. Regarding RCT outcomes, HIGH phenotype participants were less likely to be retained in the study (P = 0.02) and had higher mean self-reported withdrawal (P = 0.05) than LOW phenotype participants. A significant interaction in RCT retention was observed between phenotype (P = 0.02) and study medication (P < 0.01). Self-reported withdrawal was significant for phenotype (P = 0.02); study medication trended towards significance (P = 0.07). Results suggest patients have meaningfully different experiences of opioid withdrawal that may predict differential response to opioid pharmacotherapies during supervised withdrawal. Additional prospective research to replicate and more thoroughly evaluate withdrawal phenotype correlates and sex differences is warranted.

Project description:BackgroundDysregulation of the μ-opioid receptor has been reported in fibromyalgia (FM) and was linked to pain severity. Here, we investigated the effect of the functional genetic polymorphism of the μ-opioid receptor gene (OPRM1) (rs1799971) on symptom severity, pain sensitivity and cerebral pain processing in FM subjects and healthy controls (HC).MethodsSymptom severity and pressure pain sensitivity was assessed in FM subjects (n = 70) and HC (n = 35). Cerebral pain-related activation was assessed by functional magnetic resonance imaging during individually calibrated painful pressure stimuli.ResultsFibromyalgia subjects were more pain sensitive but no significant differences in pain sensitivity or pain ratings were observed between OPRM1 genotypes. A significant difference was found in cerebral pain processing, with carriers of at least one G-allele showing increased activation in posterior cingulate cortex (PCC) extending to precentral gyrus, compared to AA homozygotes. This effect was significant in FM subjects but not in healthy participants, however, between-group comparisons did not yield significant results. Seed-based functional connectivity analysis was performed with the seed based on differences in PCC/precentral gyrus activation between OPRM1 genotypes during evoked pain across groups. G-allele carriers displayed decreased functional connectivity between PCC/precentral gyrus and prefrontal cortex.ConclusionsG-allele carriers showed increased activation in PCC/precentral gyrus but decreased functional connectivity with the frontal control network during pressure stimulation, suggesting different pain modulatory processes between OPRM1 genotypes involving altered fronto-parietal network involvement. Furthermore, our results suggest that the overall effects of the OPRM1 G-allele may be driven by FM subjects.SignificanceWe show that the functional polymorphism of the μ-opioid receptor gene OPRM1 was associated with alterations in the fronto-parietal network as well as with increased activation of posterior cingulum during evoked pain in FM. Thus, the OPRM1 polymorphism affects cerebral processing in brain regions implicated in salience, attention, and the default mode network. This finding is discussed in the light of pain and the opioid system, providing further evidence for a functional role of OPRM1 in cerebral pain processing.

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Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.

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Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.

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