Reliability of Pupil Response to Acute Pain

The purpose of this research study is to test whether researchers can reliably measure the response pupils have when an acute painful stimulus is experienced. Changes in the size of the pupil of the eye can be an indicator of brain activity in a region of the brain that is important for feeling pain.

Study Overview

• Status: Terminated
• Conditions: Pain; Osteoarthritis

Detailed Description

There is strong rationale to support a role for locus coeruleus (LC) responsivity to acute painful stimuli in regulating speed of recovery after surgery and for LC responsivity as a mechanistic link explaining the risks for slow recovery from weak Conditioned Pain Modulation (CPM), catastrophizing cognitive style, and low enzyme activity catecholamine-O-methyltransferase (COMT) genotype. Preliminary data show feasibility to perform the proposed study.

Primary Hypothesis: An observational study of pupil responses to noxious stimuli shows strong intra-individual reliability over 8 weeks.

Key secondary hypotheses: Compared to individuals homozygous for val at the val158met site of the catecholamine-O-methyltransferase (COMT) gene, those homozygous for met will show smaller pupil responses to noxious stimuli and weaker CPM.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with athritis in the knee or hip with moderate average daily pain score

Description

Inclusion Criteria:

• Adult (18-70)
• Pain from hip or knee arthritis of moderate intensity
• American Society of Anesthesiologists physical status 1-3

Exclusion Criteria:

• Inability to complete study questionnaires
• Pregnancy
• Litigation or workers compensation related to hip or knee pain
• Taking > 50 mg morphine equivalents/day
• History of Raynaud's disease of the feet
• Psychotic disorder or a recent psychiatric hospitalization
• History of eye surgery or topical eye medications that would would directly affect pupil diameter

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Osteoarthritis; Study population to include adult men and women with osteoarthritis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Change in Pupil Diameter	pupil diameter in response to 5 second presentation of noxious heat stimuli	8 weeks
Pain Score on Visit 1	Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.	Day 1
Pain Score on Visit 2	Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.	Week 2
Pain Score on Visit 3	Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.	Month 1
Pain Score on Visit 4	Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.	Month 2

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: James C Eisenach, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2015
• Primary Completion (Actual): June 16, 2025
• Study Completion (Actual): June 16, 2025

Study Registration Dates

• First Submitted: July 8, 2015
• First Submitted That Met QC Criteria: December 8, 2015
• First Posted (Estimated): December 11, 2015

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Osteoarthritis
• Other Study ID Numbers: IRB00033891; 1P01GM113852 (U.S. NIH Grant/Contract)