Polygenic risk for alcohol consumption and multisite chronic pain: Associations with ad lib drinking behavior.

Interrelations between alcohol use disorder and chronic pain have received increasing empirical attention, and several lines of evidence support the possibility of shared genetic liability. However, research on the genetic contributions to the component processes of these complex and potentially overlapping phenotypes remains scarce. The goal of the present study was to test polygenic risk scores (PRSs) for alcohol consumption and multisite chronic pain as predictors of ad lib drinking behavior during an experimental taste test. PRSs were calculated for 209 pain-free, moderate-to-heavy drinkers (57.9% male; 63.6% White). Among White participants, the alcohol and chronic pain PRSs showed nominally significant (ps < .05) positive associations with the volume of alcohol consumed and peak blood alcohol concentration (BAC), respectively. However, associations did not survive correction for multiple comparisons. When stratifying results by experimental condition (between-subjects design: no-pain vs. pain), the alcohol PRS was significantly and negatively associated with the volume of alcohol poured, consumed, and peak BAC among Black participants randomized to the no-pain condition (all false discovery rate [FDR]p < .05). Conversely, the chronic pain PRS was significantly and positively associated with study outcomes among White participants in both the no-pain (alcohol consumed; FDRp = .037) and pain conditions (peak BAC; FDRp = .017). These findings lend partial support to the assertion that alcohol consumption in the laboratory is reflective of drinking behavior in naturalistic settings. This was also the first study to use a pain-related PRS to predict alcohol outcomes, which may be indicative of shared etiology between base and target traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pain as a causal motivator of alcohol consumption: Associations with gender and race.

Despite accumulating evidence indicating reciprocal interrelations between pain and alcohol consumption, no prior work has examined pain as a proximal antecedent of drinking. The goal of the current study was to test the effects of experimental pain induction on ad-lib alcohol consumption among moderate-to-heavy drinkers without chronic pain (N = 237; 42% female; 37% Black; M = 3.26daily drinks). Participants were randomized to either pain-induction (capsaicin + thermal heat paradigm) or no-pain-control conditions. Experimental pain induction lasted for 15 minutes, during which ad-lib alcohol consumption was assessed using an established taste test paradigm. As hypothesized, results indicated that participants randomized to the pain-induction condition poured and consumed more alcohol and reached a higher peak blood alcohol concentration than those randomized to the no-pain condition (ps < 0.05; ηp² range = 0.018-0.021). Exploratory analyses revealed the effects of pain on alcohol consumption to be most pronounced among participants who self-identified as male or Black (relative to female or White, respectively). These findings indicate that the experience of pain serves as a causal, situational motivator for alcohol consumption, and suggest that current drinkers may be susceptible to escalating their consumption of alcohol in the context of pain. Future research is needed to explicate observed differences in the effects of pain on drinking as a function of gender and race, and to extend this work to individuals with chronic pain and varying levels of alcohol use. Collectively, these findings may help inform the development of integrated treatments to address co-occurring pain and alcohol use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Family History of Alcohol Use Disorder as a Predictor of Endogenous Pain Modulation Among Moderate to Heavy Drinkers.

Family history of alcohol use disorder (AUD) is frequently endorsed by persons with chronic pain. Although individuals with a family history of AUD have demonstrated enhanced sensitivity to painful stimulation, previous research has not examined endogenous pain modulation in this population. The goal of this study was to test family history of AUD as a predictor of conditioned pain modulation, offset analgesia, and temporal summation among a sample of moderate and heavy drinkers. Adults with no current pain (N = 235; 58.3% male; Mage = 34.3; 91.9% non-Hispanic; 60% white) were evaluated for family history of AUD at baseline and pain modulatory outcomes were assessed via quantitative sensory testing. Participants with a family history of AUD (relative to those without) evinced a pro-nociceptive pain modulation profile in response to experimental pain. Specifically, family history of AUD was associated with deficits in pain-inhibitory processes. Approximately 4% of the variance in endogenous pain modulation was accounted for by family history, and exploratory analyses suggested these effects may be driven by paternal AUD. PERSPECTIVE: The current findings suggest individuals with a family history of AUD demonstrate pain modulatory function that may predispose them to the development of chronic pain. Clinically, these data may inform pain management approaches for individuals with a family history of AUD.

Method for testing sustained attention in touchscreen operant chambers in rats.

BACKGROUND: Sustained attention, the ability to detect rare and unpredictable events, is central to cognitive performance. This construct can be tested in rodents using a Sustained Attention Task (SAT), where rats are trained to detect an unpredictably occurring signal (a brief light presentation) from non-signal events. The traditional version of this task utilizes an operant chamber with a central panel light for the signal and two retractable response levers. Adaptation of SAT to the increasingly popular touchscreen operant chambers, which do not have levers or fixed lights, could enhance the versatility of the task. NEW METHOD: Here we developed a touchscreen version of SAT where the light signal is presented in the center of the touchscreen, followed by a tone to indicate the beginning of the response period. Rats indicate their choice during this period by touching their nose to one of two touchscreen response areas. The remaining parameters were kept similar to the traditional version. RESULTS: Rats acquired touchscreen SAT at a similar rate to the traditional version. As with the traditional version, shorter stimulus durations on the signaled trials reduced accuracy and the presence of a distractor (a flashing houselight) disrupted performance on the touchscreen version. COMPARISON TO EXISTING METHOD: Collectively, these data suggest that the touchscreen version is comparable to the traditional version of the SAT, and is an equally valid way of measuring sustained attention. CONCLUSIONS: Many researchers with touchscreen chambers could easily implement our modifications in order to study sustained attention.

Characterization of a Novel Chromatin Sorting Tool Reveals Importance of Histone Variant H3.3 in Contextual Fear Memory and Motor Learning.

The consolidation of short-term labile memories for long-term storage requires transcription and there is growing interest in defining the epigenetic mechanisms regulating these transcriptional events. In particular, it has been hypothesized that combinations of histone post-translational modifications (PTMs) have the potential to store memory by dynamically defining the transcriptional status of any given gene loci. Studying epigenetic phenomena during long-term memory consolidation, however, is complicated by the complex cellular heterogeneity of the brain, in which epigenetic signal from memory-relevant cells can be obscured or diluted by the surrounding milieu. To address this issue, we have developed a transgenic mouse line expressing a tetO-regulated, hemagglutinin (HA)-tagged histone H3.3 exclusively in excitatory neurons of the forebrain. Unlike canonical histones, histone H3.3 is incorporated at promoter regions of transcriptionally active genes in a DNA replication-independent manner, stably "barcoding" active regions of the genome in post-mitotic cells. Immunoprecipitating H3.3-HA containing nucleosomes from the hippocampus will therefore enrich for memory-relevant chromatin by isolating actively transcribed regions of the excitatory neuron genome. To evaluate the validity of using H3.3 "barcoding" to sort chromatin, we performed a molecular and behavioral characterization of the H3.3-HA transgenic mouse line. Expectedly, we find that H3.3-HA is incorporated preferentially at promoter regions of actively-transcribed neuronal genes and that expression can be effectively regulated by doxycycline. Additionally, H3.3-HA overexpression does not adversely affect exploratory or anxiety-related behaviors, nor does it affect spatial memory. Transgenic animals do, however, exhibit deficits in contextual memory and motor learning, revealing the importance of this histone isoform in the brain. Future studies in the H3.3-HA transgenic mouse line will define the combinatorial histone PTM landscape during spatial memory consolidation and will investigate the important contributions of histone H3.3 to the normal functioning of the brain.