Characterizing the Effects of Family History of Alcoholism on Alcohol Analgesia

Self-medication of pain with alcohol is a common, yet risky, behavior. Evidence suggests family history of alcoholism may affect the degree to which alcohol use relieves pain, but the independent contributions of expectation and conditioning have not been previously studied. Interactive effects of sex and family history are also currently unclear. This project addresses this gap in knowledge and will inform further research and clinical/translational efforts for reducing risk associated with these behaviors.

Study Overview

• Status: Completed
• Conditions: Effects of Family History of Alcoholism and Sex on Alcohol Analgesia
• Intervention / Treatment: Drug: Ethanol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Center for Pain Research and Behavioral Health at UF Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Consume at least 1 drink/month over the past 6 months

Exclusion Criteria:

• History of chronic pain
• Current use of opioids
• Current major depression
• History of any psychotic disorder
• Undercontrolled hypertension or diabetes
• History of neurologic disease
• History of serious medical illness
• History of drug or alcohol dependence, including nicotine, or a pattern of hazardous alcohol use
• Safety concerns related to MRI (for example, implants or pacing devices)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Family History Positive; People reporting at least one parent with a history of alcohol problems.	Drug: Ethanol; A beverage containing dose of ethanol individually determined to raise a participant's breath alcohol concentration up to approximately 0.08 g/dL.; Other: Placebo; A beverage that does not meaningfully increase breath alcohol concentration.
Experimental: Family History Negative; People who do not report having a parent with a history of alcohol problems.	Drug: Ethanol; A beverage containing dose of ethanol individually determined to raise a participant's breath alcohol concentration up to approximately 0.08 g/dL.; Other: Placebo; A beverage that does not meaningfully increase breath alcohol concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat Pain Threshold	Temperature of heat stimulus applied to the foot at which participant reports pain. VAS (visual analogue scale) pain intensity and unpleasantness ratings anchored from "no pain at all"/"not at all unpleasant" to "most intense/unpleasant imaginable" will be collected.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Heat Pain Tolerance	Temperature of heat stimulus applied to the foot at which participant no longer tolerates pain. VAS (visual analogue scale) pain intensity and unpleasantness ratings anchored from "no pain at all"/"not at all unpleasant" to "most intense/unpleasant imaginable" will be collected.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Heat Pain Intensity Ratings	Participant perception of pain at a temperature producing a pain rating of approximately 5 out of 10 at baseline. VAS (visual analogue scale) pain intensity ratings ranging from 0-100 and anchored from "no pain at all" to "most intense imaginable" will be collected. Higher values reflect ratings of more intense pain.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Perceived Pain Relief	Rating of relief from pain associated with consumption of the study beverage. This is a VAS (visual analogue scale) assessing perceived pain relief ranging from 0-100 and anchored from "No relief at all" to "Most profound relief imaginable". Higher scores reflect greater perception of pain relief.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Dorsolateral Prefrontal Cortex Activation	Pain-related activation in the dorsolateral prefrontal cortex associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Hypothalamus Activation	Pain-related activation in the hypothalamus associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours
Medial Prefrontal Cortex Activation	Pain-related activation in the medial prefrontal cortex associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Nucleus Accumbens Activation	Pain-related activation in the nucleus accumbens associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Periaqueductal Gray Activation	Pain-related activation in the periaqueductal gray associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Anterior Cingulate Cortex Activation	Pain-related activation in the anterior cingulate cortex associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Amgydala Activation	Pain-related activation in the amygdala associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Hippocampus Activation	Pain-related activation in the hippocampus associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Insula Activation	Pain-related activation in the insula associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Postcentral Gyrus Activation	Pain-related activation in the postcentral gyrus associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)
Thalamus Activation	Pain-related activation in the thalamus associated with application of painful heat vs. non-noxious warmth to the bottom of the right foot during fMRI acquisition. Scores are beta-weights associated with fit of activity within the region to activity predicted by convolving the canonical hemodynamic response function with the heat pain stimulus paradigm assessed using general linear modeling. Positive beta weights reflect activation associated with the stimulus paradigm, while negative beta weights reflect deactivation.	Day 1; Day 2 (Laboratory sessions will be separated by at least 48 hours.)

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Jeff Boissoneault, PhD, Assistant Professor

Publications and helpful links

General Publications

• Boissoneault J, Stennett B, Robinson ME. Acute alcohol intake alters resting state functional connectivity of nucleus accumbens with pain-related corticolimbic structures. Drug Alcohol Depend. 2020 Feb 1;207:107811. doi: 10.1016/j.drugalcdep.2019.107811. Epub 2019 Dec 24.
• Sevel L, Stennett B, Schneider V 2nd, Bush N, Nixon SJ, Robinson M, Boissoneault J. Acute Alcohol Intake Produces Widespread Decreases in Cortical Resting Signal Variability in Healthy Social Drinkers. Alcohol Clin Exp Res. 2020 Jul;44(7):1410-1419. doi: 10.1111/acer.14381. Epub 2020 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: June 8, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: pain; alcohol effects
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: IRB201800992-N; R01AA025337 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No