Phenotyping Acute Pain for Discovery Research and Directed Therapeutics

The goal of the current study is to combine existing and new tools for quantifying patient self-report to characterize changes in acute pain. The ability to quantitatively measure self-report provides behavioral pain phenotypes that can serve as the basis for clustering patients into sub-groups based on their self-report of their symptoms, eliminating observer based perceptions of patients' pain.

Study Overview

• Status: Withdrawn
• Conditions: Post op Pain
• Intervention / Treatment: Other: questionnaires

Detailed Description

Pain is a therapeutic challenge as well as a public health problem that is estimated to affect over 116 million American adults [1]; reduces quality of life; and is estimated to cost up to $635 billion annually. Growing recognition of the need for evidence-based, individual-centered treatment strategies raises expectations that health care will be improved by matching proven effective treatments with knowledge of patients' unique characteristics to optimize efficacy and safety. Essential to the goal of matching treatments to patients to enhance analgesic drug development and therapy is identification of intermediate phenotypes that capture the mechanistic complexity, genetic expression and epigenetic changes of hundreds of ongoing processes and mediators that influence treatment efficacy and safety and may form the basis for differential responses to drug therapy. The ability to identify functional variants in the genomic responses to pain and therapeutics at the sub-group and patient levels, however, has been limited to date by lack of thorough phenotyping for patients with pain.

The need for a more comprehensive understanding of human phenotypes has spawned a new method of phenotyping studies referred to as "deep phenotyping." Deep phenotyping for pharmacogenomic studies requires both breath and depth to better interpret the complexities of genomic variations that may underlie individual differences in pain report. One approach to address this complexity is to use quantitative testing of clinical features to identify more homogeneous subsets within a group of patients with a given diagnosis or characteristic. Variations in quantitative measures may identify intermediate phenotypes that are genetically less complex yet have potentially stronger signals closer to the site of gene action. In pain, quantitative testing is often termed "quantitative sensory testing", or QST.

Exclusion

1. Current or history of mental disorder or substance abuse
2. Allergy to aspirin, NSAIDS, or sulfonamide
3. Pregnant and/or nursing
4. History of peptic ulcers and/or GI bleeding
5. Concurrent use of agents which may obscure pain report, e.g., alcohol, opioids, benzodiazepines, and depressants, etc
6. Chronic use of medications confounding assessment of the inflammatory response or analgesia, e.g., antihistamines, NSAIDS, steroids, antidepressants
7. Concurrent or history of chronic diseases, e.g., diabetes, rheumatoid arthritis, liver disease, cancer, hypertension or obesity (body mass index >35)
8. Expectation of excessive surgical difficulty, resulting in a difficulty score of 5 for any tooth (determined from panoramic radiograph)
9. Subjects with extreme anxiety and who are candidates for general anesthesia or conscious sedation

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • School of Dental Medicine at East Carolina University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male or females over 18 years of age

Description

Inclusion Criteria:

1. Male and female patients aged 18 and older willing to undergo clinically indicated non-emergent oral surgery for the removal of impacted third molars with local anesthesia
2. Indicated for the removal of third molars, at least a minimum of one partial-bony impacted third molar, with a total difficulty score total of not less than 4*
3. Communicate in spoken and written English
4. Willing to undergo research observation for 4 hours postoperatively and 48 hour follow up visit
5. In good health with an ASA status of 1 or 2 by self report and review of medical history

6. Self-report of moderate or severe pain on a categorical scale with a minimum of 4 out of 10 on the numerical rating scale following the offset of local anesthesia

   • 1=erupted, 2=soft tissue impaction, 3=partial bony impaction, 4=full bony impaction, 5 = unusual surgical difficulty

Exclusion Criteria:

1. Current or history of mental disorder or substance abuse
2. Allergy to aspirin, NSAIDS, or sulfonamide
3. Pregnant and/or nursing
4. History of peptic ulcers and/or GI bleeding
5. Concurrent use of agents which may obscure pain report, e.g., alcohol, opioids, benzodiazepines, and depressants, etc
6. Chronic use of medications confounding assessment of the inflammatory response or analgesia, e.g., antihistamines, NSAIDS, steroids, antidepressants

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

open label; After the surgery and the onset of moderate-severe pain, QST and PROMIS questionnaires will be repeated. Throughout these procedures, patients will rate their pain perception using a numeric rating scale. Approximately 2-3 hours after surgery at the onset of moderate pain, the rescue analgesic (toradol) will be administered via intramuscular injection. Again, QST and PROMIS protocols will be repeated after the drug is given and when patients report pain relief. A standard naproxen dose of 500 mg will be given to patients upon leaving the clinic and they will be instructed to take one pill orally each day before returning for evaluation after 48 hours.

Other: questionnaires; The deep phenotyping of acute pain will be conducted using the oral surgery model. Before surgery, subjects will undergo QST and answer short-form questionnaires related to pain and activities of daily living.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
characterize changes in acute pain	The goal of the current study is to combine existing and new tools for quantifying patient self-report to characterize changes in acute pain	48 hours

Collaborators and Investigators

• Sponsor: East Carolina University
• Investigators: Principal Investigator: Raymond Dionne, DDS, School of Dental Medicine at East Carolina University

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2018
• Primary Completion (Actual): February 21, 2018
• Study Completion (Actual): February 21, 2018

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 23, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: 14-001670